Drinks Reception, Poster Session 1 & Meet the Editors of journal Vaccine and Vaccine X

Introduction

Updated vaccines targeting new viral variants have emerged as crucial strategies to boost immunity against SARS-CoV-2. Among these, the monovalent XBB.1.5-adapted vaccine has demonstrated a boost in both binding and neutralizing antibody responses across several viral variants suggesting a cross-protection against severe disease. Despite these promising findings, the effectiveness of the XBB.1.5-adapted booster in preventing SARS-CoV-2 infection remains limited and the booster is in several countries restricted to immunocompromised and older individuals.

Method

To determine the current prevalence of SARS-CoV-2 infections and the associated viral variants among healthcare workers (HCW) on duty, we conducted a PCR screening of 631 healthcare workers on duty at Danderyd Hospital, Stockholm, Sweden, 4-15 December 2023. Participants were recruited through the ongoing COMMUNITY healthcare worker cohort with well characterized SARS-CoV-2 infection and vaccination histories since April 2020. Diagnostic RT-PCR analysis was performed using The Novel Coronavirus (2019-nCoV) Nucleic Acid Diagnostic Kit (Sansure Biotech, Xiangya, China).  For whole genome sequencing, RNA was extracted using Nucleic Acid Extraction Kit (MGI, Shenzhen, China).

Results

During the two-week period, a total of 45 HCW out of 631 tested positive for SARS-CoV-2, representing 7.1% (95% confidence interval [CI]: 5.4-9.4%) of the cohort. The median cycle threshold value was 33.6. Notably, almost half of the participants (22/45, 49%) were asymptomatic, while 23/45 (51%) reported only mild symptoms and all participants were on duty. Whole genome sequencing revealed a dominance of JN.1 sublineages.

Conclusion

Our findings indicate a high prevalence of SARS-CoV-2 infection among HCW on duty in the hospital December 4-15 2023. Although the XBB.1.5 booster dose is unlikely to prevent infections, the high rate of infection among healthcare workers potentially escalates the transmission of SARS-CoV-2 which underscoring the necessity of ongoing administration of XBB.1.5 monovalent booster shots to vulnerable populations prone to severe disease.

Both the Increasing Vaccination Model (IVM) and Behavioral and the Social Drivers (BeSD) of vaccination framework posit provider recommendations as an important predictor of vaccination. However, demographic disparities exist in who receives provider recommendations to vaccinate against HPV, influenza, and COVID-19. Vaccine hesitancy is linked to diminished provider recommendations for both HPV and COVID-19, and recommendations related to COVID-19 are influenced by social norms and geographic variations.

The purpose of this study is to assess the prevalence of provider recommendations for COVID-19 vaccination in a rural, southern state; disparities related to sociodemographic factors (age, gender, race/ethnicity, education, income, and parent or guardian status); and associations with insurance status, social norms, COVID-19 vaccine hesitancy, and news preference. This research is unique in relation to geography (a southern state) and the attention given to news preference (a proxy for political affiliation).

In October 2022, survey data was collected from 2,201 Arkansas adults via random digit dialing. The final analytical sample was made up of 1,804 adults with a medical provider. We oversampled Black and Hispanic residents, and the sample was weighted to represent 2021 census estimates. Bivariate and multivariate logistic regressions were performed.

37% of respondents reported their provider did not recommend vaccination against COVID-19, and odds of receiving a recommendation were unequal across demographic groups. After adjusting for covariates, odds of receiving a provider recommendation increased by 66% for respondents with health care coverage, decreased by 43% - 52% for those with weaker social norms of COVID-19 vaccination, and decreased by 35% for those with vaccine hesitancy.

A large proportion of Arkansas adults did not receive a recommendation for COVID-19 vaccination and recommendations were inconsistently provided across demographic groups. Future efforts to increase COVID-19 vaccination should consider provider recommendations as a possible point of intervention.

Introduction

Human papillomavirus (HPV) is a common sexually transmissible infection causing cancers. Over 90% of cervical cancer occur following the infection. This condition is preventable. Despite the merit of the HPV vaccination in disease control, improving coverage remained challenging in Cameroon. This paper highlights the country’s vaccine introduction strategies, challenges, and progress following a single-dose gender-neutral protocol.

Methods

This August to November 2023 cross-sectional study reviewed Cameroon HPV vaccination from 2020 to June 2023. Data was collected from the district health information software. Ministry of Health Reports presented national guidelines. Data were analyzed and presented with Microsoft Excel 365. 

Results 

HPV vaccination occurred in health facilities, communities, and schools. National coverage remained less than 20%. Following the NITAG recommendations, vaccination included 9-year-old adolescent females and males from January 2023. Adhering to this recommendation, community engagement and periodic intensification of routine immunization (PIRI) led to a triple-fold increase in girls’ vaccination coverage and boy’s coverage of 34%. 

Conclusion

Although the HPV vaccination in Cameroon faced significant challenges, the gender-neutral single-dose protocol, community engagement, and PIRI marked the country’s jump in its coverage in less than six months in 2023.

In the years 2017-2022, 60% of the elderly population were vaccinated against the influenza virus at Meuhedet HMO. In the winter of 2020, it was also possible to get vaccinated with the new vaccine against the flu virus with the increased dose known as "Fluzone" (Fluzone High Dose), which contains 4 times the substance (hemagglutinin) compared to the regular vaccine that was provided to all insured members.  The new vaccine targets older population - 65 and older, whom are at greater risk of suffering from complications, as well as death from the flu virus. 

The "Fluzone" vaccine was given free of charge 

The purpose of the study is to examine the relationship between the Fluzone vaccine and the consumption of medical services (number and duration of hospitalizations, examinations, doctor's visits) compared to the control group that was vaccinated with a standard flu vaccine during the winter season of 2020-22

Comparison between two groups of vaccinated: vaccinated with the enhanced flu vaccine HD (Fluzone) compared to those vaccinated with the regular vaccine.  

The pairing between the two groups was carried out according to the following characteristics:

Age group (3 groups 65-75, 75-85, 85+), sex, health status 

Results were measured by number of visits to the GP, emergency room visits (for any reason), hospitalizations (number and duration).

The comparison shows that the study population does consume significantly less healthcare services than the control population, between 13-21 percent, depending on the service channel.

For example, a 19% difference was found in the number of hospitalization days in favor of patients who received the HD

The research proves the effectiveness of the vaccine as it appears in the research literature. This platform should construct the initial basis for the State of Israel and its patients in changing regulatory recommendations for the next flu seasons.

The Matrix 2 ectodomain (M2e) is an important influenza vaccine antigen and requires a strong adjuvant. M2 is an essential ion channel for viral replication, maturation and budding by maintaining pH across cell membranes through its proton pump activity. M2 is a clinically and commercially validated drug target because of the demonstrated efficacy of amantadine and rimantadine. However, the development of an effective, non-inferior vaccine has been elusive, partly due to a lack of immuno-potency. We found that VT-105 is immunogenic, reduces influenza viral loads and pathogenesis, and protects mice and ferrets against disease and death following two intramuscular immunizations in nanogram and microgram quantities, respectively, with or without 2% Alhydrogel® as a depot adjuvant. We used nano-sized vesicles to display six tandem genetic variants of M2e as an antigenic complex (VT-105) that represent the sequence space of the antigen.  We found that VT-105 had a protective effect against H1N1 in mice and H5N1 in ferrets following intranasal viral challenge. Antigen-specific hyperimmune sera blocked M2 ion channel function in a transfected cell fluorescent assay. Geometric mean antibody titers (GMT) ranged from 1/10,000-1,000,000 in an antigen-specific ELISA with higher GMT in mice than in ferrets. VT-105 is safe and protective in preclinical studies, reproducibly manufactured with cGMP and can be lyophilized for long-term storage at room temperature for global distribution.

Funding: HHS NIH NIAID Contract #75N93019C00060

The current failure of Moderna HIV vaccine due to excessive antigen responses leading to skin rashes has led to creating mRNA vaccine based on conserved and exposed isotopes of HIV-1 and HIV-2 and their Nef proteins to prevent latent infections due to blockage of MHC signals by the Nef proteins. We  selected the protein precursors gp160 and its resultant gp120 and gp41 for HIV-1 and the precurso gp140, and its resultant gp105 and gp36 for HIV-2 and the Nef proteins; the sequences were subjected to extensive simulations to identify B-cell and T-cell epitopes that were conserved and the B-cell epitopes that were exposed in the 3D structure. The sequences were linked through GGGG multiples and their ORF created. The mRNA molecule had the cap m7G+m3'-5'-ppp-5'-Am) as GA. The 5´-untranslated region derived from human alpha-globin RNA with an optimized Kozak sequence. The s S glycoprotein signal peptide (extended leader sequence) guided translocation of the nascent polypeptide chain into the endoplasmic reticulum. The 3´ untranslated region comprises two sequence elements derived from the amino-terminal enhancer of split (AES) mRNA and the mitochondrial encoded 12S ribosomal RNA to confer RNA stability and high total protein expression. The mRNA was formulated in a LNP formulation and tested in mice for record the binding of the target proteins using ELISA and neutralizing assays. The search for HIV vaccine is pivotal due to approximately 38.4 million people worldwide were living with HIV; and in 2022, around 1.3 million new infections reported; most infections are reported in the sub-Saharan African region where the people are least capable of affording expensive treatment of HIV. According to our calculation, an mRNA vaccine that costs less than $0.25 per dose offers the most relevant choice for the world with the hope of ending this endemic.

Several vaccines against COVID -19 have been developed and licenced to enhance the immune response against SARS-CoV-2. Similarly, infection with SARS-CoV-2 before vaccination has been shown to provide significant protection against severe infection and hospitalisation. The aim of this study was to investigate the effect of three doses of Sinopharm vaccine and SARS-CoV-2 infection on the specific immune response in 103 volunteers, measuring neutralizing antibodies, anti-S1 IgG, anti-RBD IgM, anti-N IgM, anti-N IgG antibodies and interferon γ. Our results showed that the presence of cardiovascular diseases increased the level of anti-N-IgG antibodies, while endocrinological diseases decreased the level of neutralizing antibodies and anti-N-IgG antibodies, suggesting that these diseases alter the effect of vaccine immunity. In addition, there was a significant decrease in anti-S1 IgG levels 6 months and in anti-N IgG levels 18 months post-infection, while neutralizing antibody and interferon γ levels were constant at 3, 6 and 18 months post-infection. Therefore, our results confirm the importance of hybrid immunity as the strongest and most durable compared to exclusively natural or vaccine-induced immunity. Significant positive correlations were found between humoral and cellular immunity markers: neutralizing antibodies, anti-S1 IgG, anti-N IgG and interferon γ, indicating a unique coordinated response specific to COVID-19. 

Background

While mRNA vaccines have   demonstrated efficacy in preventing symptomatic diseases among immunocompetent individuals there is limited data for immunocompromised individuals. We conducted a trial that mostly targeted People Living with HIV (PLWH) to determine whether SARS-CoV-2 infection confers robust natural immunity and synergistically enhances immunity when followed by vaccination.  

Methods

A multi-centre, randomized, double-blind trial comparing different regimens of the COVID-19 mRNA vaccine was conducted in 7 countries in Africa for 18 months. Baseline HIV status and point-of-care anti-spike serology (POCS) results were used to assign participants to four study groups. Participants received one dose of mRNA-1273 (hybrid immunity) or two doses one month apart (vaccine immunity), depending on their baseline SARS-CoV-2 sero-status. We used covariate-adjusted Cox regression & counterfactual cumulative incidence methods to determine the association of hybrid versus vaccine immunity with symptomatic Covid-19 and severe Covid-19 at 6 months. 

Results

A total of 14,237 participants were recruited of whom 83% were PLWH and 69% SARS-CoV-2 seropositive. Interim analyses suggest that PLWH with prior SARS-CoV-2 infection who received one dose of mRNA vaccine were at significantly lower risk of symptomatic COVID-19 compared with those without prior infection who received a two-dose regimen. The hybrid immunity group had a 42% lower hazard rate of COVID-19 (hazard ratio [HR] 0.58; 95% CI 0.44-0.77; p<0.001) and a 73% lower hazard rate of severe COVID-19 (HR 0.27; 95% CI 0.07-1.04; p=0.056) than the vaccine immunity group. 

Conclusion

In the initial 6 months of the study, Hybrid immunity was associated with superior protection from symptomatic Covid-19 and severe Covid-19 compared to pure vaccine immunity for all participants irrespective of HIV status.

Ordered mesoporous silicas have been proposed as vaccine adjuvants due to high surface area, pore volume, and ease of obtaining different morphologies with simple changes in synthesis conditions. In this study, four modifications were made to the synthesis conditions to obtain different morphologies. Sample 1 (S1) was synthesized at 40°C and 1000 rpm. Samples 2 and 3 (S2 and S3) were subjected to 55°C and 35°C, with stirring of 300 and 500 rpm, respectively, and left under static conditions for 24 hours. Sample 4 (S4) was synthesized under the same conditions as sample S1, except for the addition of isopropanol. SEM analyses confirmed that different morphologies were obtained, such as rope-shaped aggregated rods (S1), filiform rods (S2), hexagons (S3), and nanospheres (S4). All synthesized SBA-15 samples presented an ordered mesoporous structure, with reflections characteristic of a two-dimensional hexagonal structure with very close lattice parameter values, indicating that the silica mesostructure was preserved after the incorporation of dANA. The SAXS and NAI results indicate that, especially in samples S1 and S4, the antigen is encapsulated in the mesopores and macropores of SBA-15. Fluorescence analyses of the incorporated samples revealed the preservation of the aromatic microenvironment of tryptophan similar to the pure protein, except for sample S3, which showed a change from emission wavelengths from 320 to 356 nm, indicating the exposure of tryptophan to a microenvironment more polar. However, SRCD analyzes of all incorporated samples indicate that the secondary structure of dANA was maintained, suggesting that its function was preserved. In the immunogenic assay, the S3dANA sample stood out, presenting a significantly higher primary immune response. However, the immunogenic responses increased and became equal in the secondary response without any variation between different silicas. These results indicate that all tested SBA-15 morphologies are excellent candidates for vaccine adjuvants.

Limited information exists on the protection conferred by Coronavac (Sinovac, China), an inactivated COVID-19 vaccine. We conducted a multi-center, hospital-based, test-negative case-control study to determine the vaccine effectiveness (VE) of a complete CoronaVac regimen with or without a homologous or heterologous booster dose against hospitalized and critical COVID-19. 

Between 9 November 2022 and November 2023, we enrolled adult patients experiencing acute respiratory illness (ARI) admitted to three large government referral hospitals in the Philippines.

We collected clinical and socio-demographic data, vaccination histories, and oro/nasopharyngeal swabs for SARS-CoV-2 RT-PCR testing from eligible patients who consented to participate. Patients testing positive in at least one SARS-CoV-2 RT-PCR test were classified as cases while those testing negative were the test-negative controls. Critical COVID-19 was defined as having either respiratory failure, acute respiratory distress syndrome, sepsis/shock, or multi-organ failure.

We enrolled totally of 2,365 participants of whom 165 (7.0%) were SARS-CoV-2 positive. Over 1 year after the last vaccine dose, unmatched analysis showed that complete vaccination with CoronaVac did not protect against hospitalized and critical COVID-19 (VE: 0.69%, CI: -23.7–20.3%, p=0.9511 and VE: 5.4%, CI:17.8–24.0%, p=0.6201, respectively), but conferred 31.3% (CI: 9.5–47.9, p=0.0077) protection against death. The protection against death increased to 45.8% (CI: 18.6–63.8%, p=0.0031) with a booster dose. 

Cases were significantly older than the controls (mean age±SD: 58.12±20.15 vs. 53.41±17.60 years, p = 0.001). An age-matched analysis showed that a full regimen of Coronavac provided 61.3% (CI: 5.3– 84.2%, p=0.0376) protection against critical COVID-19, and 27.1% (CI:-25.3–57.6%, p=0.2528) against death, which increased significantly to 91.2% (CI: 30.7–98.9%, p=0.0210) and 60.1% (CI:16.4–81.0%, p=0.0150) with a booster dose, respectively. 

It shows that a primary series of inactivated COVID-19 vaccination provided protection against critical outcomes over time, which was enhanced by booster vaccination.

ChAdOx1-S is a viral vector vaccine developed by AstraZeneca. We aimed to assess the effectiveness of 1 and 2 doses of the ChAdOx1-S vaccine in reducing COVID-19-related in-hospital mortality in individuals with schizophrenia. This is a retrospective cohort study using a nationwide hospital database in Brazil. Individuals diagnosed with COVID-19 and schizophrenia were included in the study. The exposures were 0, 1, and 2 doses of ChAdOx1-S. The outcome of mortality was measured in hazard ratios (HR), calculated using multivariable Cox regression models. The study included 1,929 positive cases of COVID-19 in schizophrenia patients. After adjusting for age, socioeconomic factors, and comorbidities, we observed a significant 55% decrease in the hazard of mortality in the 2-dose vaccination group (HR 0.45, 95% CI: 0.310-0.652) compared to the unvaccinated. Surprisingly, our results did not show any significant reduction in the hazard of mortality in the 1 dose vaccination group (HR 1.278, 95% CI: 0.910-1.795). The effectiveness of two doses of ChAdOx1-S in individuals with schizophrenia aligns with findings from studies on the general population. That of one dose was insignificant. Overall, these findings are important for informing public health decisions - prioritising individuals with schizophrenia for vaccinations and managing acceptance of vaccines. 

After COVID-19, meningococcal disease increased in some countries. Respiratory viral infections may be followed by bacterial ones, a combined prevention would be interesting. Outer membrane vesicles (OMVs) of meningococci present adjuvancity and elicit antibodies against the bacterium, so we studied a preparation of SARS-CoV-2-Receptor binding domain (RBD) associated with OMVs from meningococci C:2a:P1.5 strain. BALB/c mice were immunized with three subcutaneous doses containing 0.5 (A), 1.0 (B) or 1.5 (C) μg of RBD, plus 0.5μg of OMVs and Alum. Controls were naïve mice. IgG levels and avidity were assessed by ELISA, IFN-Υ and IL-4 secretion by ELISpot. Groups A, B and C had IgG recognizing RBD and OMVs (p<0.001). Avidity-RBD was intermediary for A (46.25±26.93) and high for B (85.42 ±11.60) and C (71.05±15.38); while avidity-OMVs was high for A (81.98±5.8), B (80.62±13.12) and C (74.95±13.15). IgG1 and IgG2a ratios showed a predominance of IgG1 for RBD, the mean ratios being 5.25 for A, 3.92 for B and 5.15 for C; on the other hand, OMV response had a mixed pattern, the mean ratios being 0.82 for A, 1.67 for B and 1.91 for C. Considering the cellular response, splenocytes from all groups secreted IFN-Υ and IL-4 upon RBD or OMVs stimuli, especially group A, the only one presenting statistical difference (p<0.05). Mean spot counts for RBD-IFN-Υ/IL-4 were: 124/318 for A, 49/108 for B, 57/125 for C; for Naïve control, 13/9. Considering OMVs-IFN-Υ/IL-4, they were: 140/306 for A, 91/143 for B, 79/144 for C; for Naïve control, 10/6. Our results suggested that combining RBD with OMVs and Alum propitiates a mixed immunity, with IgG of good avidity for both antigens, Th2-biased response for RBD and Th1/Th2-response for OMVs. SARS-CoV-2 neutralization and serum bactericidal assay will provide more evidences about the functionality of the response.

IgE antibodies are typically linked to allergens or parasites, however, there is some evidence  that IgE can bind to viral antigens too. We investigated this possibility using ELISA and avidity-ELISA to detect IgE specific to Receptor Binding Domain (RBD) of SARS-CoV-2, and confirmatory experiments by IgG depletion with Protein G. Sera samples were collected throughout: before vaccination, who had confirmed COVID-19 diagnosis or not; post-vaccination with ChAdOx1 or CoronaVac (2 doses); and post-BNT162b2 booster (1 dose). Pre-pandemic sera served as control, to establish the cutoff. With institutional ethical approval and informed consent (CAAE 31924420.8.0000.0059), the study examined IgE response in a 59 females Brazilian healthcare workers cohort. COVID-19 caused mild IgE increase, while two-dose vaccination showed no significant change. However, a booster dose significantly increased IgE levels (p<0.001). When CoronaVac+BNT162b2 and ChAdOx1+BNT162b2 regimens were compared, no differences were observed. While the avidity of COVID-19-induced IgE was intermediate (mean, IQR25—75^th, 51.19, 35.95—57.78), avidity of vaccine-induced IgE was high for CoronaVac+BNT162b2 (76.64, 66.9283.26) and ChAdOx1+BNT162b2 (73.53, 59.61—81.64), without statistical difference between the regimens. Ig4, commonly induced with IgE, was higher than control only after booster (p<0.001) and correlated moderately with IgE levels (r=0.3408); however, no differences were found comparing vaccine regimens. To confirm that the IgE test results were specific, instead of unspecific binding because of high IgG concentration, 16 samples (controls, with COVID-19, without COVID-19, after two-vaccine doses and after booster) were depleted from IgG, and supernatants were assayed, corroborating ELISA results. Using a surrogate-neutralization assay that considers all immunoglobulin classes and Spearman’s rank correlation, we observed that, after two ChAdOx1 or CoronaVac doses, IgE levels and avidity correlated well with neutralizing indexes (r=0.7125 and r=0.7967, respectively). More research is needed to understand the role of IgE in viral infections.

Antiviral IgA antibodies in respiratory tract are superior to circulating IgG antibodies in preventing infection at the mucosal surface. However, the role of innate immune signals required for induction of mucosal IgA to SARS-CoV-2 infection is unknow. Here we show that hamsters recovered from ancestral SARS-CoV-2 infection are cross-protective against heterologous SARS-CoV-2 alpha, gamma, delta, and omicron variants. Intranasal vaccination with inactivated whole virus vaccine completely protects hamsters from heterologous SARS-CoV-2 alpha variant infection. In addition, we find that intranasal vaccination of mice recovered from a mouse-adapted SARS-CoV-2 infection with unadjuvanted spike protein stimulates secretion of high levels of respiratory anti-spike IgA. MyD88 and MAVS are essential for induction of memory IgA response following unadjuvanted spike vaccination in mice recovered from the SARS-CoV-2 infection. These findings provide a useful basis for developing effective mucosal vaccines against SARS-CoV-2 infection.

Nursing home residents (NHR) are a generally frail population experiencing reduced immunity and high risk for severe COVID-19. Documenting the immune response and clinical protection after COVID-19 vaccination by collecting real-world data is crucial in this demographic, as they were typically underrepresented in vaccine trials. Therefore, we conducted a national sero-epidemiological surveillance study in 1640 NHR and 1368 nursing home staff (NHS) in Belgium to assess SARS-CoV-2 antibodies and identify breakthrough COVID-19 cases up to two years post-COVID-19 vaccine implementation. We used serological rapid tests and dried blood spots to assess the presence and quantity (by ELISA) of anti-spike 1 SARS-CoV-2 IgG, respectively. Serology and clinical data were collected at two-monthly intervals after primary course vaccination and three-monthly intervals after first booster administration. After primary course vaccination, infection-naïve NHR exhibited poor antibody responses, with >10 times lower antibody concentrations than in infection-primed NHR, and 10% (95% CI 7-14%) vaccine non-responders. Antibody concentrations among NHR and NHS significantly waned within six months after primary course vaccination (p<0.001). Contrastingly, after booster administration, infection-primed and infection-naïve NHR presented equal antibody concentrations (p>0.05). Moreover, antibody concentrations among NHR did not significantly decrease within the nine-month follow-up period after booster administration (p>0.05), showing a more durable response. We found that breakthrough infection cases had significantly lower pre-infection antibody concentrations than non-breakthrough cases (p<0.001), with 87% (95% CI 60-91%) of cases having antibody concentrations below 3000 IU/mL, suggesting an antibody correlate for protection. With our study, we demonstrated the importance and feasibility of collecting real-world data to guide vaccination strategies, strengthening future pandemic preparedness efforts. By identifying specific risk groups for poor vaccine response, like infection-naïve NHR, vaccine approaches can be tailored, including timely boosters, to ensure sustained immunity among vulnerable populations. 

The Opa proteins are a family of 11 heterogeneous phase-variable outer membrane proteins which undergo antigenic variation through inter- and intra-strain recombination between alleles. Opa proteins significantly contribute to the adherence/invasion of epithelial cells and neutrophils through binding to human carcinoembryonic antigen related cell adhesion molecule (CEACAM) receptors 1, 3, 5 and 6. We have developed a multivalent investigational vaccine, Ng-GMMA, which contains Opa proteins amongst others. 

To define the flavors and array of Opa proteins expressed by a panel of gonococcal strains, closed genome sequences for each were determined with long read sequencing and Opa-expressing sub-populations were estimated with deep sequencing. A Luminex-based assay was developed to measure the interaction of the diverse gonococcal strain with recombinant CEACAM 1, 3, 5 and 6. The ability of the Ng-GMMA vaccine mouse antisera to inhibit bacterial interaction/binding to the distinct CEACAM human ligands as well as to inhibit bacterial adhesion conducted using cellular epithelial models including Detroit 562 (for oropharyngeal tissue), Ect-1 (for ectocervix tissue ) cell lines was assessed. 

The binding of gonococcus to the CEACAMs was shown to be Opa-specific and anti-sera from our investigational Ng-GMMA antisera differentially inhibited the interaction of the representative panel of strains with diverse CEACAM ligands, presumably depending on the alleles of Opa expressed by the diverse strains. Bacterial adhesion inhibition experiments showed that our Ng-GMMA vaccine is able to inhibit bacterial adhesion both to Ect-1 and Detroit 562 cell lines.

Therefore, we have developed innovative assays to determine antibody functional activity around the inhibition of Opa-CEACAM interactions driving host-pathogen behaviors. Initial results demonstrate that mouse antisera from our Ng-GMMA vaccine elicits responses that can inhibit interaction with CEACAMs and adhesion to urogenital and oropharyngeal epithelial mucosa likely through, but not limited to, anti-Opa antibodies.

Susceptibility to medically attended influenza B virus (IBV) infections by the B/Victoria and B/Yamagata lineages varied by birth year during their co-circulation between 2000-2020. We have recently demonstrated that differential cross-reactivity to the IBV haemagglutinin underpins lineage-specific susceptibility between birth cohorts, in a manner consistent with differential exposure to these antigenic lineages in the first decade of life. This implies the existence of highly conserved neutralising epitopes within each lineage despite ongoing antigenic drift. Characterising such epitopes that underlie immunological imprinting could inform vaccine design.

We collated serum samples collected between 2009-2012 from individuals born in 1954-1960 (Ancestral lineage-imprinted, n=22), in 1970-1975 (B/Victoria-imprinted, n=24) and in 1987-1995 (B/Yamagata-imprinted, n=23). We performed haemagglutination inhibition (HAI), live virus microneutralization and ELISA assays with possibly encountered viruses (circulating prior to sample collection) and future unencountered viruses (circulating after sample collection) from different lineages. Sequence analysis was used to identify conserved sites within each lineage. Site-directed mutagenesis, reverse genetics and absorption experiments were used to identify amino acid residues affecting lineage-specific imprinting. 

Biases in reactivity consistent with differential early life exposure between birth cohorts were evident in HAI titres and partly in microneutralization titres but not in ELISA titres to full-length HA or the HA1 domain. Consistently, we identified amino acid residues near the receptor-binding site of HA that were conserved within, but not between, B/Victoria or B/Yamagata from 1987 until 2019. A subset of these residues within the major antigenic loops were shown to underpin imprinted cross-reactivity to future isolates.

The conservation of major antigenic sites on HA within, but not between, each antigenic lineage underlies immunological imprinting to IBV. Since these conserved epitopes can confer neutralisation across an entire antigenic lineage despite ongoing antigenic drift, their identification provides a rational pathway towards universal IBV vaccine development.

Age and sex are the two most significant characteristics, among several, that influence the strength and effectiveness of the immune response to vaccinations. Sex-disaggregated analysis of humoral response to vaccinations, including COVID-19 vaccines, is rarely available and frequently controversial. Healthcare workers (HCWs) are the target population for vaccination against coronavirus disease (COVID-19) as they are at  high risk of exposure and transmission of pathogens to patients.

This study aimed to evaluate sex-based differences in anti-S/RBD (Receptor Binding Domain) responses at various time points following the second dose of mRNA COVID-19 vaccine, in 521 HCWs, naïve to SARS-CoV-2 infection, accounting for immunization age. X-chromosome associated and/or sex hormones modulated microRNAs, which regulate multiple immune functions, and sex hormones—important players in the sex difference in immune response—as well as the potential relationship between anti-S/RBD antibody levels and these factors were statistically analyzed.

Significantly higher anti-S/RBD response to the COVID-19 vaccination was found in female HCWs, and a significant and more abrupt decline in response with time was observed in women than that in men, and in younger age groups than in those over 50. Statistically significant, novel positive association of testosterone plasma levels and higher anti-S levels in male HCWs was found, suggesting its potential role as a sex-specific predictive biomarker of response to the COVID-19 vaccination in young men. Two circulating microRNAs (miR221-3p, mir-148-3p) that are highly expressed in females were found to positively correlate with anti-S/RBD levels after COVID-19 vaccination.

In conclusion, understanding the sex-based differences in humoral immune responses to vaccines may potentially improve vaccination strategies and optimize surveillance programs for HCWs. In addition, identification of sex-specific markers predictive of immune response to vaccination will contribute to customize health surveillance programs for healthcare professionals, accounting for sex disparities

The opportunistic pathogen Pseudomonas aeruginosa (Pa) causes severe nosocomial infections, especially in immunocompromised individuals and the elderly. Increasing drug resistance, the absence of a licensed vaccine and increased hospitalizations due to SARS-CoV-2 have made Pa a major healthcare risk. To address this, we formulated a candidate subunit vaccine against Pa (L-PaF), by fusing the type III secretion system tip and translocator proteins with LTA1 in an oil-in-water emulsion (ME). This was mixed with the TLR4 agonist (BECC438b). Lung mRNA sequencing showed that the formulation activates genes from multiple immunological pathways eliciting a protective Th1-Th17 response following IN immunization. Following infection, however, the immunized mice showed an adaptive response while the PBS-vaccinated mice experienced rapid onset of an inflammatory response. The latter displayed a hypoxic lung environment with high bacterial burden. Finally, the importance of IL-17 and immunoglobulins were demonstrated using knockout mice. These findings suggest a need for a balanced humoral and cellular response to prevent the onset of Pa infection and that our formulation could elicit such a response.

To protect older adults against influenza A virus (IAV) infection, innovative vaccination strategies are imperative to overcome the decrease in protective immune response with age. One approach involves the boosting at middle age of CD8⁺ T cells, that were previously induced by natural infection. At this stage, the immune system is still fit. Given the high conservation of T-cell epitopes within internal viral proteins, vaccination inducing responses against these proteins may confer lasting protection against evolving influenza strains at older age. Potentially, this can reduce the high number of influenza immunizations currently required as well. At the time of booster vaccination in middle-aged adults, some individuals may have been more recently exposed to IAV than others, which could affect the T-cell response. We therefore investigated the fundamental question how the interval between the latest infection and booster immunization influences the CD8⁺ T-cell response. To model this, female mice were first infected with IAV (H7N9) at either 6 or 9 months of age. Subsequently, mice received a heterosubtypic infection booster (H1N1) at 12 months, representative for vaccination at middle age. Prior to booster infection, 6-month-primed mice displayed lower IAV-specific CD8⁺ T-cell responses in the spleen and lung than 9-month-primed mice. Both groups were better protected against the subsequent heterosubtypic booster infection compared to naïve mice. Notably, despite the difference in CD8⁺ T-cell responses between the 6-month- and 9-month-primed mice, we observed comparable responses after booster infection, based on IFNγ production, IAV-specific T-cell frequencies and repertoire diversity. Lung-derived CD8⁺ T cells of 6- and 9-month-primed mice expressed similar levels of tissue-resident memory T-cell markers 30 days post booster infection. These data suggest that the IAV-specific CD8⁺ T-cell response after boosting is not influenced by the time post priming. 

Immunogenicity of the first generation of vaccinia viruses (VACV), such as NYCBH strain, was well proven in the campaign to eradicate smallpox. However, their adverse effects limited their use as vaccines, including as a vector for recombinant vaccines. VACV E3 protein is a potent inhibitor of PKR and RNase L pathways and deletion of the E3L gene (VACVΔE3L) renders the virus highly attenuated. VACVΔE3L was shown to completely protect mice against ectromelia virus challenge. In this study, we modified the host range of NYCBH VACVΔE3L , that only replicates in murine cells, by replacing its host range gene K3L with taterapoxvirus K3L ortholog TATV037 (NYCBHΔE3L/TATV037) to make the virus replication competent in both murine and human cells. Based on the VACVΔE3L/TATV037 platform, we constructed recombinant virus expressing SARS-CoV-2 spike (S) and nucleocapsid (N) proteins (NYCBH/S/N). Following a single intramuscular immunization (i.m.), the NYCBH/S/N induced protection against infection of the ancestral strain and several major variants of concern (VOCs) of SARS-CoV-2 in hamsters, including alpha, delta and omicron. The immunization significantly reduced virus load in lung and upper respiratory tract, improved recovery time and reduced weight loss. Moreover, no adverse reaction was observed in hamsters following i.m. immunization with the NYCBH/S/N and the control virus without SARS-CoV-2 S and N. In summary, we demonstrated that the NYCBHΔE3L/TATV037 is a promising platform for development of recombinant vaccines.

Very little is known about the impact of intramuscular vaccination on mucosal immune responses. Specifically, whether a mucosal antibody response is induced by COVID-19 vaccination. We recently reported that COVID-19 vaccination elicited a transient mucosal sIgA response in healthy adults that rapidly wanes in most, but not all vaccinees. Moreover, vaccinees who had breakthrough infections post-vaccination had lower systemic (serum) IgA antibodies to SARS-CoV-2 spike/RBD. Here, we aimed to characterize the salivary antibody response to vaccination in a cohort of healthy children, and how this response compares to adults. We recruited n=100 healthy 5-11-year-old children and acquired saliva samples at baseline, and various time points post-dose 1 and post-dose-2. We observed significant increases in salivary SARS-CoV-2-specific IgG and IgA levels postdose-1 compared to baseline. Pediatric postdose-1 SARS-CoV-2-specific salivary IgG and IgA levels were 3x and 2x higher than adults, respectively. Salivary IgG levels were further boosted post-dose-2 and, similar to adults, IgA levels dropped significantly compared to post-dose-1, with only 46% of pediatric subjects remaining positive. We believe that the oral microbiome may be one factor influencing the IgA response, and the capacity of certain subjects to retain this response post-dose 2. We have collected preliminary data which shows that anti-RBD IgA levels correlate with levels of IgA-coated bacteria in saliva. We also see that subjects who experienced a delayed breakthrough infection (4-6 months post-dose 2) had higher levels of IgA and IgG-coated bacteria in their saliva at baseline compared to subjects who experienced an early breakthrough infection (1-4 months post-dose 2). We are currently conducting preliminary animal experiments to help us better understand the relationship between the anti-commensal response and the post-vaccine mucosal IgA response in the upper respiratory tract.

id.DRIVE is a public-private-partnership of pharmaceutical companies and research organisations joining in a consortium to facilitate the conduct of observational studies on infectious diseases, vaccines, related preventive measures, therapeutics and diagnostics in Europe. id.DRIVE expands from COVIDRIVE initiated in 2020 to collect real-world data on brand-specific COVID-19 vaccine effectiveness (CVE). 

As of January 2024, the consortium included six pharmaceutical companies (AstraZeneca, Janssen, GSK, Novavax, Valneva, Pfizer), and two non-industry partners (FISABIO, P95). 

The first study, launched in September 2021, was a multi-country, multi-centre, hospital-based test-negative case-control design to monitor brand-specific CVE against hospitalisation due to laboratory-confirmed SARS-CoV-2 infection in severe acute respiratory infection (SARI) adults, including CVE by time since last dose and by SARS-CoV-2 variant (EUPAS42328).

In total, 21 hospitals in Austria, Belgium, Germany, Italy, and Spain have actively enrolled patients. As of 28 February 2024, id.DRIVE recruited 11,843 SARI patients, including 3,921 (33%) COVID-19 cases. Median patient age was 72 years (55% male); 62% of patients had ≥2 chronic conditions. 

Recruitment for studies sponsored by Janssen and AstraZeneca was completed on 28 February and 01 March 2023, respectively. Progress (Novavax), interim (AstraZeneca & Janssen) and final (AstraZeneca) study reports were submitted to the European Medicines Agency. 

A surveillance study for the monitoring of viral respiratory infections in adults hospitalised for SARI is planned for June 2024 (EUPAS1000000012). SARS-CoV-2, respiratory syncytial virus (RSV), influenza virus and potentially 15-17 additional pathogens will be detected by RT-PCR. This 12-month sentinel study will capture data covering all seasons and builds the foundation for a sustainable study-ready system that can be activated to evaluate effectiveness of vaccines and related pharmaceutical products. 

The id.DRIVE platform delivers high quality epidemiological studies with shared data collection for regulatory use. It enables collaborative generation of real-world evidence through a sustainable European research network.

Introduction: Italy has made ground-breaking progress in the field of adult vaccination, being one of the first to propose a life-course vaccination schedule, thus broadening historical focus on children to include adults. The aim of the review is to exchange knowledge and best practices to enhance adult immunization strategies across Europe, sharing Italy's innovative approaches and discussing the challenges faced due to its fragmented healthcare system.

Methods: This review is based on information shared during a 2-day Adult Immunization Board (AIB) meeting held in Florence, Italy, in December 2023 (www.adultimmunizationboard.org). Invited experts were identified through a thorough review of the scientific literature. During the meeting, national and region-specific topics on adult immunization in Italy were discussed by the AIB advisors with local experts; talks were given by local academics, healthcare professionals, public health representatives, civil society and policymakers, covering all aspects of Italy’s adult immunization, from policymaking to vaccine acceptance and coverage.

Results: The country’s National Vaccination Plan 2023-2025 establishes clear coverage targets, immunization priorities, and initiatives to minimize disparities. All vaccines listed in Italy’s vaccination schedule are part of the Essential Levels of Healthcare (LEAs) and thus provided free of charge to residents. Nonetheless, the fragmentation of Italy’s National Health System following the constitutional reform of 2001 has introduced greater complexity and regional discrepancies in immunization, particularly affecting vaccine procurement, delivery, and administration. Italy also grapples with decreasing vaccine confidence, significant data gaps, and the challenge of reaching underserved populations. 

Conclusion: This work describes Italy’s adult immunization system, from policy to implementation and monitoring. Sharing Italy's experiences in adult immunization is beneficial for two reasons: it enables Italy to appraise its achievements and hurdles, guiding future policy and implementation decisions, and provides a blueprint for other European countries to glean lessons and optimize their own vaccination strategies for adults.

The microbiota is known to play a crucial role in the development and activation of various immune responses. Our previous research has demonstrated that symbiotic bacterial sensing by the Nod2 receptor contributes to the efficacy of mucosal immunization with antigen and cholera toxin. However, the potential toxicity of cholera toxin limits its human clinical trial. To address this challenge, we conducted a screening of other adjuvants that depend on the presence of the microbiota. Among the candidates derived from microbial components, TLR4 and TLR7 agonists showed a synergistic effect with the microbiota in inducing adaptive immune responses to nasal immunization. Specifically, Imiquimod, a TLR7 agonist, synergized with MDP, a Nod2 ligand, in inducing immune responses such as IL-12p40 and IL-6 production from bone marrow derived dendritic cells and follicular helper T cell differentiation, as well as high affinity antibody production from immunized mice. Notably, the Imiquimod-MDP combination elicited potent protection against influenza and SARS-CoV-2 infections. Furthermore, we isolated some bacteria from the nasal cavity of healthy donors and measured their Nod2-stimulating activity using a reporter cell line. Staphylococcus aureus, with notable Nod2-stimulating activity, showed higher synergy with Imiquimod than Staphylococcus epidermidis, while the synergistic effects by Imiquimod plus bacteria disappeared in Nod2-knockout mice. Moreover, pretreatment with S. aureus enhanced the protective effect of Imiquimod-mediated vaccination against influenza infection as compared to S. epidermidis. These findings suggest that the Imiquimod-MDP or the Imiquimod-bacteria combination could be a novel and promising complex adjuvant for intranasal vaccines. Our research highlights the importance of improved mucosal immunization strategies and their potential to facilitate effective immune responses.

Introduction. Functional antibody methods are laborious and dependent on the properties of the virus strain. Methods. We developed an in-house fluorescent multiplex immunoassay (FMIA) that measures IgG against one neuraminidase and four haemagglutinin antigens from recent seasonal influenza A vaccine strains (A(H1N1)pdm09 strains A/Victoria/4897/2022 and A/Victoria/2570/2019, A(H3N2) strains A/Darwin/9/2021 and A/Cambodia/e0826360/2020) simultaneously from a single well. We tested all antigens for cross-reactions and assessed assay repeatability and reproducibility. We analysed vaccine responses from 161 sera collected in 2021-2024 from annually vaccinated healthcare workers. To estimate background reactivity, we analysed 99 sera collected in 2005 from 1-5-year-old children. The IgG concentrations of vaccinated subjects were compared to live virus microneutralisation titers. Results. None of the five antigen-conjugated beads had significant cross-reactions with one another when tested in 1- versus 2-plex (coefficient of variation (CV)<11%) nor when all were combined into a 5-plex (CV≤11%). The assay had good reproducibility (CV<9%) and repeatability within (CV<4%) and between days (CV<14%). N1-conjugated beads were unable to detect antibodies in the sera of the vaccinated compared to the background. The assay could distinguish samples collected from healthcare workers who had received seasonal influenza vaccines containing pdm09 H1 from pre-H1N1-pandemic samples. The correlation between FMIA and microneutralisation test was excellent for A/Victoria/2570/2019 (Pearson correlation 0.91, P<0.001) and good for A/Cambodia/e0826360/2020 (R=0.52, P=0.0018). Discussion. The FMIA enables the evaluation of vaccine responses against several viral antigens simultaneously and is suitable for rapid evaluation of vaccine responses from large samples. The assay was however unable to distinguish responses within the same subclass (H1 or H3), although there was no notable assay cross-reactivity between 1- and 5-plex results. The FMIA is likely to identify a larger number of antibodies binding to different antigenic epitopes compared to functional methods, resulting in greater cross-reactivity within subclasses.

Introduction: We report vaccine effectiveness (VE) estimates of mRNA and inactivated COVID-19 vaccines among healthcare workers (HCWs) during the Omicron subvariant-dominated 5^th to 7^th COVID-19 waves in Hong Kong between February 2022 and March 2023.

Methods: HCWs were recruited from hospitals and clinics across Hong Kong from June 2020–May 2021 and followed up biannually with blood sample collections. VE of 2–4 doses of vaccination with mRNA or inactivated COVID-19 vaccines against SARS-CoV-2 infections confirmed by PCR or rapid antigen tests was estimated with a Cox proportional hazards model that allows for changes in vaccination status throughout the follow-up period with adjustments for age, sex, comorbidities, direct contact with COVID-19 cases, and previous infections.

Results: We included 1636, 974, and 832 of 1742 HCWs for VE estimation for waves 5–7, respectively. The median age was 41–45 years, and 72–74% were female. Most participants (96%) reported providing direct care to COVID-19 cases at enrolment. During the 5^th wave, which was predominated by the Omicron BA.2 subvariant (Feb – June 2022), compared to unvaccinated HCWs, the VE among HCWs was estimated as follows: two doses of BNT162b2 -25% (95% CI: -469%, 11%), two doses of CoronaVac -14% (95% CI: -299%, 68%), three doses of BNT162b2 81% (95% CI: 52%, 93%), three doses of CoronaVac 79% (95% CI: 40%, 92%). Additional doses beyond the primary series offered additional protection (VE between 10% and 91%) against Omicron BA.5 and a combination of Omicron BA.2 and BA5 sublineages in waves 6 and 7, respectively.

Discussion: Vaccination with booster mRNA or inactivated COVID-19 vaccinations offered substantial protection to HCWs against Omicron subvariant infections during the 5^th­ to 7^th wave compared to unvaccinated HCWs and those only vaccinated with a primary series (two doses) of either the mRNA or inactivated vaccine.

A prospective universal vaccine for SARS-CoV-2, with the potential to defend against various viral variants, offers hope for enhancing worldwide readiness for future pandemics. Development of optimal universal vaccine requires a stringent set of criteria that surpasses traditional vaccine models. Beyond merely targeting specific viral strains, it should provoke a broad and long-lasting immune response, tackling multiple viral components to combat antigenic changes effectively. Ideally, a one-time vaccination providing lifelong protection, both systemic and mucosal, would streamline vaccine distribution. Furthermore, ensuring affordability is crucial to guarantee fair access, particularly in economically disadventaged areas. 

The aim of the project is to develop a novel antigen, tri-RBD-S2, and explore an alternative vaccination approach against SARS-CoV-2 infection. Our strategy involves utilizing a self-assembling chimeric recombinant protein that combines the receptor binding domain (RBD) from SARS-CoV-2, incorporating key mutations from the Delta and Omicron variants, with two segments of the Spike (S) protein 2 subunit to develop tri-RBD-S2 trimeric particles. These particles will present essential epitopes from the native S protein. We will test the antigen in a murine model. We hypothesize that administering the tri-RBD-S2-based vaccine intranasally will elicit superior immunity compared to intramuscular injection. Leveraging conserved viral epitopes, we anticipate the vaccine will confer broad and long-lasting protection against SARS-CoV-2, representing a significant stride towards a universal vaccine against the virus.

For the protection of humankind from continuously changing seasonal and occasional pandemic influenza and coronavirus outbreaks, broadly-reactive vaccines are essential. Harnessing T-cell responses targeting conserved internal viral proteins could contribute to protection from a broad range of influenza and coronaviruses, by clearing infected cells through recognition of shared virus epitopes.  

We investigated novel T cell–inducing nucleoside-modified messenger RNA (mRNA) vaccines against influenza and SARS-CoV-2 viruses. The mRNA-Flu vaccine encodes conserved nucleoprotein, matrix protein 1, and polymerase basic protein 1 of an H1N1 influenza virus. mRNA vaccines against SARS-CoV-2 encode nucleoprotein (mRNA-N) or nonstructural proteins -5, -12, -13, -16 (mRNA-nsp) of SARS-CoV-2.  

Utilizing animal models to mimic both naïve and virus-experienced scenarios, we evaluated prime-boost regimens to mimic real-world vaccination strategies. In ferrets, mRNA-Flu not only elicited but also boosted broadly-reactive T-cell responses across systemic and mucosal compartments. Notably, vaccination of influenza-experienced ferrets conferred enhanced protection against a heterosubtypic highly pathogenic avian influenza infection. Similarly, in HLA-A2 transgenic mice, mRNA vaccines against SARS-CoV-2 induced robust T-cell responses in relevant tissues. However, upon challenge with a pathogenic Beta SARS-CoV-2 variant, vaccine-associated enhanced disease was observed, with more prominent weight loss and lung pathology in omicron-experienced mice. 

These findings underscore the potential of mRNA vaccines encoding conserved internal viral proteins for broad immune protection against influenza. Yet, they also raise caution regarding vaccine-associated enhanced disease, urging further mechanistic studies to inform the development of safe and effective broadly-reactive vaccines.

Introduction 

In November 2023, the UK’s Joint Committee for Vaccination and Immunisation advised 4CMenB vaccination for men-who-have-sex-with-men (MSM) with increased risk of gonorrhoea acquisition. High numbers of sexual partners increases risk but not all sexual health patients may disclose this information. Diagnostic history or attending due to partner notification are alternative markers for increased risk.

Methods

We extended a risk-structured deterministic compartmental model of gonorrhoea transmission to assess the impact and cost-effectiveness of strategies vaccinating MSM at sexual health services in England: 

• upon diagnosis (VoD), 
• VoD plus notified partners (VoN) 
• VoD plus those diagnosed with gonorrhoea in the last year (VaH)
• VoD plus those reporting ≥5 partners in the last year (VaR)

We considered two-dose vaccine efficacies of 20% and 40%, a 1.5-year duration of protection, and the same uptake as HPV vaccination. We calculated each strategy's net monetary benefit (NMB), which is the value of health gains with a quality-adjusted life year (QALY) valued at £20,000 minus net costs of vaccination, with discounting at 3.5%p.a., over 10 years, for a vaccine costing £18/dose administered. Positive NMB indicates cost-effectiveness.

Results

At 20% efficacy, VoD, VoN, VaH and VaR averted 29.8(95% credible interval:  15.5-50.0), 35.6(18.6–60.4), 37.6(17.6–72.1), and 67.8(25.2–149.4) thousand cases over 10 years respectively, and were cost-effective strategies with 83%, 86%, 86%, and 90% probability respectively.  At 40% efficacy, strategies averted approximately 95% more gonorrhoea cases, and all strategies were always cost-effective.

Discussion

Even if vaccine efficacy is modest, vaccinating MSM at increased risk of gonorrhoea acquisition is likely to be cost-effective. While VaH and VoN have a lower impact than VaR, both strategies have a higher impact than VoD alone, and are more likely to be cost-effective. These strategies should be considered when information on partnership numbers is unknown.

Background

People affected by haematological malignancies face higher risk of morbidity and mortality from vaccine-preventable diseases. However, completion rates of post-treatment vaccinations are sub-optimal. Informing service innovation according to the needs and preferences of the target population may improve vaccine uptake. This study aimed to understand barriers, enablers and preferences to vaccination and novel vaccines among this special risk group. 

Methods

A two-stage mixed methods study in Australia. First, exploratory semi-structured interviews were undertaken with blood cancer patients and transcribed verbatim. Inductive template analysis was used to develop codes, categories, themes; then the coding frame was mapped to the COM-B model of behaviour change to identify barriers and enablers. Following, a survey was developed from interview results and disseminated online to a national, cross-sectional, non-probabilistic sample of people affected by haematological malignancies who had received treatment. Data were analysed using descriptive statistics and qualitative content analysis as appropriate. 

Results

Twenty people participated in an interview, and 87 responded to the survey. Interviews found that while people understood benefits of vaccination, there were substantial barriers relating to opportunity (care coordination, travel, time, and financial costs) and motivation (concerns regarding intervention and appointment fatigue, potential side effects and injury, and vaccine development processes (particularly novel technologies such as mRNA)). Enablers identified included personalised information, automated care, and hybrid and shared care models. Survey responses confirmed that financial and time costs of vaccinations were considerable barriers, and motivational concerns regarding fear of side effects and reduced immunogenicity were common. While people saw potential convenience benefits of shared care models, remaining linked into specialist care was crucial. Findings were synthesised to produce recommendations. 

Conclusion

This study has generated world-first evidence investigating the preferences of people affected by haematological malignancies regarding vaccination to inform more acceptable, accessible, and appropriate models of delivery.

Introduction:                                                        

Vaccines may act to reduce infection acquisition (V_acquisition), symptom development (V_symptoms), infection duration (V_duration) (accelerating natural clearance), or infectiousness (V_infectivity). The relative effects of these pathways may differ between measured outcomes in trials of different designs, and on population-level impact (i.e. incidence and prevalence). Furthermore, a vaccine will likely have more than one action, creating uncertainty about how observed trial efficacy relates to expected population impact. We examine how the choice of trial outcome measure and frequency of measurement, can alleviate this.

Methods: 

Mathematical modelling of gonorrhoea natural history and transmission among men-who-have-sex-with-men examined the relationships between (i) different vaccine actions, (ii) observed efficacy results in trials of different designs, and (iii) the population-level impact of vaccination implemented at scale.

Results 

For vaccination at scale, individual properties V_acquisition and V_infectivity have strong effects, and V_duration a weaker effect, in reducing transmission. If V_acquisition, V_infectivity, or V_duration are 0.5, transmission is reduced by 50%, 50% , and 44% respectively. However, V_symptoms promotes transmission by prolonging the average infection, because symptoms prompt care-seeking whereas asymptomatic infection is detected by screening or unless natural recovery occurs first: V_symptoms=0.5 increases transmission by 21%. 

Trial designs incorporating frequent screening and reporting vaccine efficacy against symptomatic and asymptomatic diagnoses separately, reduced uncertainty in underlying vaccine properties and gave more precise estimates of population impact, compared to if only a combined efficacy estimate against all diagnoses was reported. Trials without screening showed the greatest uncertainty between efficacy at trial and population impact, potentially undervaluing impactful vaccines or overvaluing weakly-effective vaccines.

Discussion

V_acquisition is detected through decreased diagnoses, but assessing V_symptoms and V_duration requires distinguishing symptomatic and asymptomatic infections. Trial designs incorporating this, better capture the true underlying vaccine properties, and so yield more accurate estimates of impact at scale.

Despite the availability of many commercialized vaccines in the market, SARS-CoV-2 remains a challenge. With the newly emerging variants, there is a constant demand for a better vaccine that will provide broader neutralization efficiency to all and upcoming variants of the SARS-CoV-2. Here we show that the trimeric RBD of the spike protein expressed from a circular RNA (circ-RNA) backbone elicits a potent neutralizing antibody response, providing robust protection against the SARS-CoV-2 in mice. The circ-RNA vaccine candidate induced a T_H1-biased antibody and T-cell response. We further show that the circ-RNA^RBD-Delta provides a protective immune response against Wuhan and Delta variants but not to the omicron variant while the circ-RNA^RBD-omicron protects the omicron variant only. A combination of circ-RNA^RBD-Delta and circ-RNA^RBD-omicron produced an effective protective response against all variants of the SARS-CoV-2. A comparison of Circ-RNA with self-amplifying mRNA (SAM) technology showed similar immune response. Given the possible side effects of the SAM vaccine and the ease of producing Circ-RNA, the later may be a better for RNA vaccine.

[Aim]

Currently, the mRNA vaccines against SARS-CoV-2 induces a robust systemic immune response. However, its efficacy wanes several months after vaccination and it does not induce mucosal immunity to prevent respiratory infections. Therefore, it is desired to develop a vaccine that induces mucosal immunity and effectively protect against wide range of mutant strains over the long term. This study was designed to evaluate the efficacy of intranasal immunization with spike (S) protein of SARS-CoV-2 combined with carboxyvinyl polymer (CVP; S-CVP), a viscous agent, to induce more effective intranasal immunity.

[Methods]

The S-CVP was inoculated intranasally into mice and the induced immune response were compared to those induced by S protein mixed with alum as an adjuvant (S-alum). The humoral and cellular immune responses elicited by vaccination were measured. To evaluate the protective effect of S-CVP, vaccinated mice were challenged with SARS-CoV-2 and the viral replication and lung inflammation were measured. Cross-protection of S-CVP against omicron BA.1 and BA.5 was also investigated. In addition, long-term immunity was evaluated. 

[Results]

S-CVP inoculated mice had significantly higher binding and neutralizing antibodies in the mucosal epithelium and serum than mice treated with S-alum. In addition, S-CVP significantly suppressed the viral replication, inflammatory cytokines production, and pneumonia severity. It also demonstrated cross-protection against omicron BA.1 variant. Moreover, S-CVP-induced immunity persisted for at least 15 months and was cross-protective against SARS-CoV-2 omicron BA.5 variant.

[Discussion]

We demonstrated that intranasally administered S-CVP induced potent humoral and cellular immune responses and protected mice against SARS-CoV-2 infection. In addition, S-CVP was effective in inducing long-lasting immunity against a wide range of SARS-CoV-2 variants, ranging from the early pandemic strains to the Omicron BA.5 variant in mice. Therefore, intranasal vaccination with the co-administration of CVP and antigen may be a promising candidate vaccine against viral infections of the respiratory tract.

Background: In the face of increasing SARS-CoV-2 infections among the vaccinated, hybrid immunity has become more common among a growing portion of the population. We investigated the surge in infections from 2022 to 2023 within a cohort of healthcare workers that had received three COVID-19 vaccine doses and assessed the impact of hybrid immunity on antibody levels.

Methods: The cohort had received the latest vaccine dose at the turn of the year 2021 and 2022. Serum samples were collected in autumn 2022, spring 2023, and autumn 2023. We measured IgG antibodies against the nucleoprotein (N-IgG) and spike protein (S-IgG) and neutralizing antibodies (nAb) against the original virus and Omicron variants XBB.1.5 and EG.5.1. We examined the occurrence of infections among the cohort both based on N-IgG levels and on a questionnaire survey.

Results: A total of 54/66 (82%) subjects had contracted SARS-CoV-2 infection prior to sampling in autumn 2022, 61/66 (92%) before spring 2023, and 63/66 (95%) before autumn 2023. Those with hybrid immunity had significantly higher (>8-fold) S-IgG levels at all time points compared to those with vaccine-induced immunity only (P<0.0001). The increases in N-IgG concentrations indicated that some participants had experienced reinfections. In individuals with hybrid immunity, the S-IgG concentrations and nAb titers against Omicron variants were higher. Notably, individuals with reinfections showed the highest concentrations of Omicron-specific S-IgG and nAb.

Conclusions: Within the follow-up cohort, the proportion of individuals with infections increased gradually, and by the end of 2023, the majority had acquired hybrid immunity. Considering the substantial enhancement due to infection in immune response conferred by the three-dose vaccine regimen, it was projected that booster vaccines would not yield significant additional benefits for the healthy adult population throughout the fall and winter of 2023/2024.

Dengue virus (DENV) infection is one of the most important public health concerns in tropical and subtropical regions. Currently, Dengvaxia® and Qdenga®, a live-attenuated platform, are approved dengue vaccines in use in many countries. However, these vaccines elicit imbalanced immune responses against all dengue serotypes and retain limitations due to Antibody-dependent enhancement (ADE). In comparison to live attenuated vaccine, mRNA vaccine is safer, more effective, and offer simplified production processes. We therefore developed several constructs of the nucleoside-modified mRNA vaccine encoding the pre-membrane and envelope protein (prM/E) of DENV1 designated as WT prM/E. To minimize the ADE production, we combined the mutation of F108A at the fusion loop epitope or using the pr region from Japanese encephalitis virus (JEV) to the encoding region. Furthermore, envelope domain III (EDIII) was replaced with a consensus sequence from all dengue serotypes in order to generate neutralizing antibody (NtAb) against all serotypes. The immunogenicity, including humoral and cell-mediated immune responses, was examined in BALB/C mice. Groups of BALB/C mice were immunized two times in three-week intervals with 1 μg, 2.5 μg, or 10 μg mRNA-LNP vaccine. WT prM/E induced higher NtAb titers against dengue virus serotype 1 in a dose-dependent response compared to other constructs. Moreover, DENV1 mRNA vaccines generated dengue-specific T cell responses against envelope protein of DENV1, particularly 2.5 μg WT prM/E and prM/E combined with F108A. It is anticipated that one of these DENV1 mRNA-LNP vaccines will be proposed as a promising prototype vaccine for future development of a tetravalent dengue vaccine, offering protection against dengue virus infection.

Background: Oral polio vaccine (OPV) has been associated with reduced all-cause child mortality, suggesting that OPV has beneficial non-specific effects (NSE). Since the mid-1990s more than 2,500 national campaigns with (C-OPV) have administered more than ten billion doses of OPV to eradicate wild poliovirus. The effect on overall mortality has not been assessed but it is presumably small, given that poliovirus is close to being eradicated and polio rarely cause mortality.

Methods: We used Health and Demographic Surveillance System data to compare all-cause child mortality after and before C-OPVs in Cox proportional hazards model adjusted for other campaign interventions, calendar year and season. We distinguished between C-OPV administered alone and co-administered with other campaign interventions, e.g. Vitamin A supplementation and measles vaccine.

Results: In Bandim, urban Guinea-Bissau, between 2002-2014 C-OPVs were associated with a 25% (95% CI: 15-33%) reduction in all-cause mortality. In Chakaria, rural Bangladesh, between 2004-2019, the estimate was a 31% (10-48%) reduction. In Nouna, rural Burkina Faso, between 2012-2016, C-OPV reduced mortality and hospitalisations (composite outcome) by 36% (6-56%). Limited effect was observed on all-cause mortality (5% (95% CI: -4-13%)) in the most recent study from Navrongo, rural Ghana, between 1996-2015. However, C-OPVs had been more frequent in Ghana and C-OPV effects differed by age groups and historical period. No similar effects were found when OPV was co-administered with other intervention or for other campaign interventions.

Conclusion: OPV is planned to be stopped in 2027, but this expected deadline remains a moving target. Based on the existing evidence of the NSEs of OPV, cessation of OPV may paradoxically increase child mortality. It is urgent that we fully understand the NSEs of OPV to find ways to mitigate the potential negative impact of cessation. One drop may have saved more lives than anyone could have imagined.

Mathematical models have a well-established role in understanding of the impact of vaccination strategies. Compared to other modeling approaches, agent-based models allow for detailed simulation of specific scenarios, and enable comparison with a broader range of data. Over the last several years, we developed a suite of ABMs that have seen widespread use for modeling different vaccine-preventable diseases, including COVID-19, HPV, and STIs. Recently, we codified the principles common across these models into a standalone tool called "Starsim" (http://starsim.org). One of the primary use cases for Starsim probing questions around preferred product characteristics, optimal vaccine delivery platforms, and impact levers.

Starsim contains modules representing diseases, contact networks (sexual/respiratory/maternal), demographics, and interventions. It is written in pure Python and is completely free and fully open-source under the MIT license. Vaccine impact can be flexibly modeled with full control over the vaccine products and delivery strategies as well as background interventions, and the model also produces estimates of resource requirements. These choices are intended to lower the barrier for adoption and modification by researchers.

Since 2020, we have trained >200 people to use Starsim tools. The approach has proven simple enough that most users were able to quickly learn these tools, and flexible enough to model users' requested policy scenarios. For example, we were able to rapidly develop an HIV-HPV model that could answer questions about the effectiveness of targeted HPV vaccination, as well as a suite of models used to analyze vaccine stockpiling targets for controlling outbreaks. 

Most vaccine modeling studies quantify a vaccine’s impact as the reduction in burden of the diseases targeted by that vaccine. In contrast, the Starsim framework is designed to examine the broader impact of vaccination on coinfections and comorbidities: factors that have become increasingly important for designing and implementing optimal vaccination strategies.

While SARS-CoV-2 has transitioned to an endemic phase, infections caused by newly emerged variants continue to result in severe, and sometimes fatal, outcomes or lead to long-term COVID-19 symptoms. Vulnerable populations, such as people living with HIV, face an elevated risk of severe illness. Emerging variants of SARS-CoV-2, including numerous Omicron subvariants, are increasingly associated with breakthrough infections. Adapting mRNA vaccines to these new variants may offer improved protection against Omicron for vulnerable individuals.

In this study, we examined the humoral and cellular immune responses before and after administering adapted booster vaccinations to people living with HIV, alongside a control group of healthy individuals. Four weeks following booster vaccination, both groups exhibited a significant increase in neutralizing antibodies and cellular immune responses. Notably, there was no significant difference in immune response between people living with HIV and the healthy controls. However, immune responses in both groups declined rapidly three months post-vaccination.

These findings demonstrate the efficacy of the adapted vaccination regimen. The results suggest that regular booster immunizations may be necessary to sustain protective immunity.

Global health impact of climate change is reshaping ecosystems, spreading infectious diseases to new regions, and increasing human susceptibility. The appearance of Japanese encephalitis (JE) in south-eastern Australia highlights this evolving health-risk landscape, as warmer weather and flooding create ideal conditions for mosquito breeding. Declared a Communicable Disease Incident of National Significance in March 2022 a comprehensive outbreak response was mounted across human and animal health sectors, with vaccination a key element. JE vaccination swung from being an expensive option for intrepid international travellers to a government-funded domestic disease prevention strategy targeting people who lived or worked in newly endemic JE-affected areas of Victoria and New South Wales.

Safe vaccination was supported through development of self-paced eLearning modules to rapidly upskill and bolster Victoria’s immunisation workforce in the public health response. The model enabled timely communication of program content changes in response to heightened risk during Victoria’s flood event, expansion of eligible risk cohorts, and evolving clinical advice from the Australian Technical Advisory Group on Immunisation. Approximately 1,000 health professionals completed the eLearning in the first 3-months. The content also informed the development of national training and clinical guidance.

In that first season, JE vaccination in Victoria quadrupled from a pre-outbreak average 528 doses-per-month as an exotic travel vaccine to see over 33,000 outbreak doses delivered, with Imojev® the dominant brand. The adverse event notification rate to Victoria’s vaccine safety service was 0.3 per 1,000 doses including five reports of vaccine administered in contraindication to immunocompromised persons. No safety signals or serious adverse events were observed despite several expansions of the vaccine eligibility criteria, affecting all age cohorts. 

Australia’s domestic JE vaccination program demonstrated the agility and flexibility crucial for public health response amidst climate change-driven shifts in disease patterns, mosquito habitats and expanding areas of disease endemicity. 

Context: In the U.S., Human papillomavirus (HPV) is the most common sexually transmitted infection with men who have sex with men (MSM) having higher prevalence relative to non-MSM. Incidence of HPV is doubled among people living with HIV (PLWH). In the United States, 91% of anal cancers each year are attributable to any HPV type and anal cancer risk is substantially higher among MSM who are living with HIV. The current study leverages cohort data of MSM living with HIV to examine HPV vaccine outcomes and anal cancer awareness.

Method: Analyses include a baseline sample of MSM from Philadelphia, Pennsylvania and Honolulu, Hawaii (n=199). Descriptive, bivariate, and logistic regression analyses examine HPV-related outcomes including associations between demographics, psycho-social predictors.

Results:  In this sample, 14.8% reported being diagnosed with HPV and 34.48% of those diagnosed reported receiving current treatment. Concerning vaccination, 68.18% reported having heard of HPV, 43.22% reported hearing about anal cancer, 17.09% reported receiving an HPV vaccine and16.08% reported intending to receive an HPV vaccine. Resilient coping was positive associated with HPV awareness, HPV vaccine receipt, and HPV vaccine intent. Reporting “other sexual identity” and “other racial identity” were associated with lower likelihood to be aware of HPV. Reporting white racial identity was associated with lower HPV vaccine uptake.  

Conclusion and Discussion: Though a majority of participants are aware of HPV, few PLWH reported HPV vaccine receipt or intent. It is critical to increase HPV vaccine distribution and HPV-related cancer screening among PLWH.

Alarming rise in transmission of avian influenza virus and the rapid evolution of seasonal influenza strains warrants development of broadly-reactive influenza vaccine strategies. CD8 + T cells recognizing conserved viral proteins are promising targets for vaccination against influenza A virus (IAV). The induction of strong immune responses via peptide vaccination is limited by their weak immunogenicity. One strategy to overcome this is by vaccination with chemically enhanced altered peptide ligands (CPLs), which have improved MHC-binding and immunogenicity. However, it remains unknown how peptide modification affects the resulting immune response. We aimed to characterize the immune response to 4 different CPLs (derived from the immunodominant influenza M1_58–66 epitope (GILGFVFTL)) which had been validated to improve binding affinity towards HLA. In HLA-A2*0201 transgenic mice, CPL-vaccination led to higher T-cell frequencies, but only a small percentage of the induced T cells recognized the GILG-wildtype (WT) peptide. CPL-vaccination resulted in a lower richness of the GILG-WT-specific T-cell repertoire and no improved protection against IAV-infection compared to GILG-WT peptide-vaccination. One CPL even appeared to enhance pathology after IAV-challenge. CPL-vaccination thus induces non-relevant T cells not targeting the original peptide, which may lead to potential unwanted side effects. Our findings indicate that CPLs might not be beneficial for immunodominant epitopes, however there may be potential application for subdominant epitopes. Nevertheless, safety concerns regarding this technology must be addressed in any future studies.

Introduction

Current prophylactic vaccines, developed using L1 VLPs (Virus-Like Particles of the major papillomavirus capsid protein L1), are not effective in treating individuals already infected with HPV including cervical cancer and other HPV-associated diseases. Several prominent advantages of mRNA vaccines against COVID-19 lead to change the new spotlight for vaccine R&D. Therefore, we aim to develop the novel therapeutic mRNA vaccine by targeting the potent oncoprotein E7 by using HPV16 as a prototype and determined therapeutic efficacy in C57BL/6 mice bearing with TC-1 Luc tumor model.

Method

We generated modified nucleoside encoding HPV16 E7 encapsulated lipid nanoparticle (LNP). The protein was modified to reduce its oncogenicity and fused with IgE as a signal sequence. Female C57BL/6 were prior implanted subcutaneously with TC-1 Luc cells and followed by HPV16 E7 mRNA-LNP immunization at 10 ug/dose for 2 doses at day 3 and 10. Therapeutic efficacy was monitored by daily by measuring bioluminescence signal tumor volume. Specific T cell responses were also analyzed.

Results

Mice immunized with HPV16 E7 mRNA-LNP significantly activated HPV specific cytotoxicity effector T cell responses by increasing percentage of IFN-γ, Granzyme B, TNF-α and IL-2 producing T cells compared to those immunized with NSS (p<0.05). In addition, mice vaccinated with HPV16 E7 mRNA-LNP markedly reduce tumor size at approximately 89.9% at 17 days post-implantation compared to mice immunized with NSS when 5x10⁴ cells of TC-1 Luc were used. However, completely inhibition of tumor growth (100% tumor free mice) was observed when TC-1 Luc cells were reduced to 1x10⁴ cells.

Conclusion: Our results highlight the potential therapeutic role of HPV16 E7 mRNA-LNP vaccine. This vaccine prototype could be applied with other high risk HPV genotypes in treating HPV driven cancers and HPV-associated diseases.

Each year hospital Accident and Emergency (A&E) departments experience substantial attendances related to respiratory illness. Those with underlying co-morbidities are at higher risk of poorer outcomes from respiratory infection. We sought to document the annual burden of adult respiratory attendances accounting for the proportion occurring in those with underlying co-morbidities in England.

An analysis was performed on A&E attendances in adults ≥18yrs relating to respiratory illness over the 7-year period 2013/14-2019/20 using Hospital Episode Statistics (HES) data. The attendances were stratified by age (18-34yrs, 35-49yrs, 50-64yrs, 65-74yrs, 75-84yrs, ≥85yrs) and selected underlying co-morbidities (cardiac disease, chronic liver disease, chronic lung disease, chronic renal disease, and diabetes mellitus). The proportion of attendances that resulted in subsequent hospital admission were also investigated.  

Analysis showed a year-on-year rise in annual attendances, with a 2.2-fold increase from 2013/14 (347,567 attendances) to 2019/20 (749,976 attendances). The selected underlying comorbidities accounted for 43.3% in 2013/14 compared to 51.2% in 2019/20.   

Overall, 47% of the A&E attendances occurred in those aged ≥65yrs. Of those with the selected underlying co-morbidities, the largest proportion of attendances were found in those aged 75-84yrs (28.3%). In total, 32.8% of the A&E attendances analysed resulted in subsequent hospital admission. Analysis showed the co-morbidities contributing most to respiratory attendances were cardiac disease (34.41%), chronic lung disease (34.0%) with chronic liver disease contributing the least (4.9%).

Limitations include HES coding no longer being used for A&E attendances post 2019/20. The data studied included all respiratory attendances, than those solely caused by a respiratory pathogen. This analysis only included a selection of co-morbidities and is not comprehensive.

A&E attendances due to respiratory illness’ are increasing. Improving uptake of vaccines targeting respiratory pathogens in eligible adults including those in risk groups could help relive the burden on A&E departments.

Introduction: Immunocompromised individuals are more vulnerable to severe COVID-19 and may not receive the same level of protection from vaccinations as those with intact immune systems. We studied neutralizing antibody (NAb) responses against various SARS-CoV-2 variants after a bivalent booster dose targeting the Omicron variants BA.4/BA.5 within a group of patients with Severe Chronic Kidney Disease (CKD). 

Methods: The patients (n=10), who had previously received five to six doses of COVID-19 vaccine, were given their next dose (the sixth or seventh) of the Comirnaty Original/Omicron BA.4/5 vaccine in spring 2023. Serum samples were collected before this dose and one month after. We measured NAb titers against the vaccine viruses (original virus, Omicron BA.4 and BA.5), and more recent Omicron variants XBB.1.5, and EG.5.1. Previous SARS-CoV-2 infections were also detected based on IgG antibodies against nucleoprotein. 

Results: Bivalent BA.4/5 booster dose increased NAb geometric mean titers (GMTs) for all studied viruses (range 2.5 to 5.0-fold). The rise was significant (p<0.05) against Omicron BA.4 and BA.5 in those patients who had not been infected. As expected, NAb GMTs were higher for vaccine viruses and lower for Omicron variants XBB.1.5 and EG.5.1. Three of the patients had been infected and their NAb levels were 2.8–10.0-fold higher both before and after booster vaccination compared to those who had not been infected. 

Discussion: The bivalent BA.4/5 booster notably increased NAb titers, especially against vaccine viruses, in CKD patients, indicating improved immunity in these patients, whose response to the vaccine typically remains inadequate. Subjects with hybrid immunity demonstrated consistently higher NAb responses, even against newer Omicron variants XBB.1.5 and EG.5.1. 

The Coronavirus Disease 2019 (Covid-19), caused by virus SARS-CoV-2, has claimed and affected millions of lives since its emergence. Number of studies have suggested that influenza vaccination can provide protection against COVID-19. This study evaluated the impact of 2021/2022 seasonal influenza vaccination on the immune response to the booster dose of anti‑SARS‑CoV‑2 vaccine in a cohort of healthy individuals. A total of 113 healthy donors were enrolled, of which 74 met the criteria for analysis after receiving the booster dose of SARS-CoV-2 vaccine without a diagnosis of COVID-19 or significant co-morbidities Participants were vaccinated first with the anti-influenza tetravalent vaccine and then with the anti-SARS-CoV-2 vaccine or with the anti-SARS-CoV-2 vaccine alone. Blood was collected before and 4 weeks after each vaccination, and 12 weeks after vaccination against SARS-CoV-2, and were analyzed for influenza- and anti-spike-specific antibody titers and for in vitro influenza- and SARS-CoV-2-neutralizing ability. Subjects who received both influenza and Covid-19 vaccinations were more responsive to the SARS-CoV-2 vaccine compared to those who received SARS-CoV-2 vaccine alone, with sustained anti-spike antibody titers up to 12 weeks post-vaccination. Anti-nucleoprotein antibody titer was also evaluated to assess whether asymptomatic COVID-19 infection had occurred. In addition, the immune response to the influenza vaccine was assessed by analyzing hemagglutination inhibition titers and virus neutralization ability against the 4 antigens included in the vaccine. Individuals were stratified as high or low responders. High responders to influenza vaccination showed increased antibody titers against SARS‑CoV‑2 vaccine both after 4- and 12-weeks post-vaccination. On the contrary, individuals classified as low responders to influenza vaccine were less responsive also to the SARS-CoV-2 vaccine. These data indicate that both external stimuli, such as influenza vaccination, and the host's intrinsic ability to respond to stimuli are important in the response to vaccines and diseases.

Human papilloma virus (HPV) infections are a major health burden worldwide. Infections with high-risk HPVs can induce various oral and anogenital cancers, being responsible for >95% of cervix carcinomas. Currently approved vaccines act in a preventive, but not in a therapeutic manner. We aim to develop a therapeutic HPV vaccine based on the viral vector VSV-GP to induce HPV-specific T cell responses and consequently targeting persistent HPV infection prior to malignant transformation. Our therapeutic vaccine candidate is based on the chimeric viral vector VSV-GP, expressing a vaccine antigen cassette consisting of HPV16 E2, E6, and E7. Since replication of VSV-GP results in a transcriptional gradient of viral genes, we inserted the HPV16 vaccine antigen cassette at the first or fifth position within the viral genome and showed that the position 1 construct was superior for induction of HPV-specific T cell responses. The induction of local HPV-specific cytotoxic T cell responses in the female genital tract may be beneficial for the prevention of cervical cancer. We therefore further characterized T cell responses after systemic versus local immunization or a combination of both in more detail. HPV-specific T cells were not only induced systemically but also locally in the vaginal mucosa. However, both systemic and intravaginal immunization induced high anti-vector T cell responses in the vaginal tract that might limit efficacy of subsequent boosting. This was especially true for two subsequent intravaginal immunizations. Notably, at least one local application seemed to be beneficial for induction of HPV-specific tissue resident memory T cells in the genital tract, which are associated with the efficacy of therapeutic HPV vaccines. Taken together, VSV-GP is a promising candidate as therapeutic HPV vaccine as the vector combines a favorable safety profile with a robust induction of HPV-specific T cell responses at an entry side of HPV.

Background. Studies on vaccines against several pathogens indicated that following vaccination females develop higher antibody responses than males. Since few studies reported sex-disaggregated COVID-19 vaccine efficacy data, clear conclusions on immune responses induced by COVID-19 vaccines in females and males are not yet conclusive. We previously showed that integrase-defective lentiviral vector (IDLV) delivering an optimized Wuhan Spike protein with cytoplasmic tail truncation, D614G mutation, double proline substitutions and mutated furin cleavage site, was highly immunogenic in mice, eliciting persistent cross-reactive neutralizing antibodies (nAbs). Here we compared the immunogenicity of IDLV expressing the optimized Spike from either Wuhan (IDLV-S-Wu) or Omicron BA.1 VoC (IDLV-S-BA.1) in both female and male mice. 

Methods. IDLV-S-Wu and IDLV-S-BA.1 were produced by plasmid co-transfection in 293T cells. Spike expression was confirmed by confocal microscopy and Western Blot. BALB/c mice (6 females and 6 males per group) were immunized once with either IDLV-S-Wu or IDLV-S-BA.1. Kinetics of anti-Spike Ab response was assessed by ELISA and neutralization assays.

Results. Spike proteins were efficiently expressed in transduced cells and incorporated on IDLV particles. Male and female mice immunized with either IDLV-S-Wu or IDLV-S-BA.1 developed persistent anti-RBD IgG with similar kinetics. Vaccination elicited homologous nAbs that persisted until 24 weeks p.i. in females, while decreased after the peak response in males. IDLV-S-Wu immunization induced cross-nAbs against VoC, while IDLV-S-BA.1 elicited cross-nAbs against the Omicron VoC, showing strongly reduced cross-reactivity against Wuhan, Delta and Beta VoC, regardless of sex.  Higher cross-nAb titers were detected in females compared to males regardless of the vector used.

Conclusions We confirm that IDLV delivering optimized Spikes represent an efficient vaccine against SARS-CoV-2. We showed that Wuhan induced a better cross-neutralizing response than Omicron BA.1 derived Spike, as observed in vaccinated humans. Moreover, nAbs, but not binding IgG, are significantly different between females and males. 

During the SARS-CoV-2-pandemic, innovative mRNA-vaccines were approved with unprecedented speed. The COVID-19 mRNA-vaccines consist of mRNA coding for SARS-CoV-2-spike-glycoprotein, enclosed by lipid nanoparticles (LNPs). The vaccines protect from severe disease and allowed for the transition from a pandemic to an endemic phase. The risk-benefit assessment was always in favor of the vaccines, but rare adverse reactions, e.g. myocarditis, were reported, of which the pathogenesis is still elusive.

The goal of our study is to understand how mRNA vaccines modulate the immune system to decouple safety related effects from efficacy-defining mechanisms. We aim to understand the increased risk of myocarditis. Potential explanations could be an aberrant expression of spike-protein in the myocardium, a direct negative impact by LNPs on cardiomyocytes or a generalized inflammatory response.

An animal trial was conducted, in which guinea pigs were immunized with mRNA-vaccine or empty LNPs. Two and seven days after each immunization animals were sacrificed to perform gross pathology and to collect organ-samples. Samples were analysed by qRT-PCR and histopathology for cytokine and SARS-CoV-2-spike-expression and for inflammatory processes in the tissue.

Preliminary data show elevated levels of the inflammatory chemokines, CCR3 and CXCL10, at the injection site and the heart. High amounts of IL-1, CCL3 and CXCL10 were found in spleen and liver. Vaccine-spike-mRNA was detected in large quantities at the injection site, spleen and liver but only at low levels in the heart. Immunohistopathology indicates inflammatory processes at injection site, heart, spleen and liver shortly after immunization. We aim to find out, if these inflammations can be correlated with the presence of mRNA-vaccine-particles..

In view of their versatility and immunogenicity mRNA vaccines have become an indispensable part of our pandemic-preparedness-armamentarium. However, any potential safety issue has to be elucidated and resolved. Our efforts will contribute to this process and thereby enhance general vaccine acceptance.

Background

Any remaining doses of live multi-dose vaccines must be discarded 6 hours after reconstitution and practices of only opening them if a certain number of children are present, persist in many countries. In Guinea-Bissau, this results in health facilities (HFs) limiting  vaccinations with BCG, measles, and yellow fever vaccines to predefined days. If too few children are present, the caregivers are told to return another day but not guaranteed vaccination then. We aimed to describe experiences with the restrictive vial opening policy (RVOP) of caregivers and health care workers (HCWs) in rural Guinea Bissau. 

Methods

A qualitative study nested within an ongoing trial was conducted to explore views, perceptions and experiences of caregivers of vaccine-eligible children and HCWs on the national vaccination programme and RVOP. Data were collected during July-October 2023 through focus group discussions (FGDs) and semi-structured interviews in the regions Biombo, Oio, and Farim in Guinea-Bissau. A thematic networks analysis was performed.

Results

No caregivers (n=29, 4 FGDs) or HCWs (n=9), expressed negative perceptions of vaccines. Most caregivers reported several difficulties in seeking and obtaining vaccinations, especially multi-dose vaccines, including vaccine stock-outs, HCW strikes, transportation to HFs, and waiting time at the HFs. All described wanting vaccinations for their children and many stated returning to the same HFs repeatedly was their only option for seeking vaccinations. Most HCWs perceived the RVOP as a logical result of limited vaccine availability but described how balancing vaccine uptake and dose wastage negatively affected their sense of purpose and job satisfaction. To optimize the vaccination process, many participants recommended that the RVOP be abandoned and more resources allocated to the HFs. 

Conclusions

Navigating within the RVOP burdens both caregivers of vaccine-eligible children and HCWs. The RVOP is one of several persisting barriers for vaccinations in rural Guinea-Bissau that should be addressed.

Herpes simplex viruses (HSV) establish lifelong latent infection from which the virus can periodically reactivate to cause recurrent painful skin lesions, as well as more serious neurological disorders and disseminated disease in newborns. HSV-2 is the primary cause of genital herpes. HSV-1, typically associated with oral lesions, can also cause genital infection but has a much lower risk of recurrences. No licensed vaccines exist for HSV-1 or HSV-2, for either prophylactic or therapeutic use, and treatment relies on antiviral medications that are only partially effective. We report the results of a preclinical efficacy study of a live attenuated vaccine candidate derived from a recombinant HSV-1 virus. Guinea pigs were intradermally administered two doses of RVx1001, in two different formulations (n=11 each), 3 weeks apart. Monitoring of clinical signs, weight, and body temperature indicated no safety concerns in response to either formulation of RVx1001. Following the challenge with HSV-2 (MS), evaluation of clinical manifestations for 14 days post inoculation (dpi) demonstrated the efficacy of both formulations of RVx1001 against acute disease. Recurrent genital lesions and viral load in vaginal swabs were quantified beginning at 15 dpi to assess protection against symptomatic recurrences and asymptomatic viral shedding; both parameters were reduced in vaccinated animals. Neutralization assays with sera collected pre and post-vaccination, as well as post-challenge with HSV-2, showed high anti-HSV titers in vaccinated animals. Finally, viral load was quantified in lumbosacral dorsal root ganglia to assess the vaccine’s impact on the ability of HSV-2 to establish latent infection. The differences in efficacies between the two formulations are discussed. The development of a safe and effective vaccine that protects against HSV genital disease would have broad public health impacts, with the potential to alleviate painful and stigmatizing symptoms in up to 50 million people in the US and a half billion worldwide.

Background: For the first time, the effect of one and two doses of adjuvanted influenza vaccines on toll-like receptors (TLRs) in accordance with postvaccination antibody titers (AT) in patients with common variable immunodeficiency (CVID) was studied and compared (primary vaccination with one vs. two doses, primary vs. repeated vaccination). Materials and methods. 6 patients with CVID were vaccinated with one dose of quadrivalent adjuvanted influenza vaccine during 2018–2019 and 2019–2020 influenza seasons, 9 patients – with 2 doses of trivalent adjuvanted influenza vaccine during 2019–2020. Expression of TLR3, TLR8, TLR9, geometric mean titers (GMТ) and rate (GMR) of antibodies were measured. Results. In the group of patients vaccinated with one dose, cases of an increase in antibody titer in individual patients are isolated, while in the group of patients vaccinated with two doses it was shown that the chance of a 2-fold increase in AT for all considered strains in a result of vaccination with two doses is 9.3 times higher (Mantel-Haenszel odds ratio) than with one dose (p= 0.02), regardless of the strain. Moreover, there was a statistically significant increase in the expression of all examined intracellular TLRs registered on granulocytes (p < 0.05), monocytes and lymphocytes, regardless of the immunization scheme, that probably indicates the activation of innate immune parameters and nonspecific protection against pathogens, and an increase in the immune response.

Brazil offers a wide range of vaccines universally and free of charge through the National Immunization Program. However, since 2016, vaccination coverage has fallen below target. Brazilian municipalities, responsible for executing immunization actions involving various processes, including management, have faced difficulties and challenges. The objective of this study was to diagnose the challenges to immunization actions in Brazilian municipalities, aiming to identify the main problems related to the distribution, storage, application, and registration of National Immunization Program vaccines.

This cross-sectional study was conducted in the second half of 2023, utilizing a self-administered questionnaire sent via email to all Brazilian municipalities. A total of 4,951 responses were received, representing 88.9% of the total number of municipalities. Descriptive statistical analysis was performed on the data.

The main problem identified is related to the recording of administered doses in official information systems, notably due to internet instability and problems with vaccine distribution logistics. Key bottlenecks included delays in receiving vaccines, inadequate vial quantities, and failure to receive vaccine doses by municipalities. Significant issues with immunization professionals were also noted, including work overload, high turnover rates, staff shortages, and insufficient training. Furthermore, vaccine storage problems such as power outages, limited infrastructure investment, and equipment maintenance were highlighted.

The results reveal regional disparities. In the North Region, characterized by the Amazon, municipalities face challenges in distribution logistics, internet access, inadequate storage infrastructure, and professional shortages. In the Southeast and South, more industrialized regions, vaccine hesitancy emerged as the primary issue.

Respiratory infections due to influenza are a significant public health concern. The WHO estimates around 1 billion cases of influenza infections annually worldwide, with 3-5 million severe cases and 290,000-650,000 influenza-related deaths (Global Influenza Strategy 2019-2030, WHO). One way to control the spread of influenza infection is through vaccination with a focus on eliciting a nasal IgA response. We have developed an oral recombinant nonreplicating adenoviral vector (rAd5) vaccine platform that elicits strong mucosal immunity in humans. This rAd5 vaccine platform encodes various vaccine antigens which are expressed in host epithelial cells to elicit potent immunity. Previously, we demonstrated that expressing influenza hemagglutinin (HA) provided protection against a related influenza challenge primarily by eliciting an antigen specific mucosal homing IgA B cell response (Liebowitz et al, Lancet ID, 2020). Here, we investigated next generation rAd5 influenza vaccine candidates in preclinical studies, aiming to provide better protection against various subtypes of influenza A virus (IAV). Our new constructs showed a 40% increase in surface antigen expression in human intestinal epithelial cells compared to the original vaccine.  Mice primed and boosted with the new candidates, either with a full-length HA or a stem only HA based on the A/California/04/2009 virus (H1N1), developed 10-fold higher robust and cross-reactive IgG antibodies towards homologous (H1) or heterologous (H5) HA proteins by Day 42, compared to the original vaccine. Ferrets are immunized to test protection in an influenza challenge model.   In summary, our next-generation rAd5-HA vaccines have the potential to elicit more broadly protective immune response against various subtypes of IAV, leading to more effective influenza prevention and control.

Background: COVID-19 vaccination was the key to the control of the pandemic. Although high immunization rates were achieved in the general population, vulnerable populations facing social-structural challenges did not have access to vaccines. There is a need to understand the extent and determinants of vaccine disparity to better address them going forward.

Methods: We conducted weekly events at single-room occupancy dwellings in Vancouver’s inner city, offering COVID-19 vaccines and related information. Participants completed a survey regarding their COVID-19 vaccination status as well as a qualitative interview to assess their knowledge about COVID-19 infection. 

Results: From 01/21 to 08/23, we collected data from 892 participants: median age 45 years (IQR 36-55) years, with 317 (35.5%) females and 285 (31.9%) self-identifying as Indigenous. Within the cohort, 512 (57.4%) reported unstable housing, and 441 (49.5%) were active injection drug users. Regarding COVID-19 vaccinations, 235 (26.3%) remained unvaccinated, 119 (13.3%) had received one dose, 432 (48.4%) had received two doses, and 106 (11.8%) had received at least three doses. Variables such as age (AOR 2.28, 95% CI 1.37-3.80, p<0.001) were significantly associated with higher odds of vaccination uptake. Conversely, unstable housing was significantly associated with lower odds of vaccination uptake (AOR 0.53, 95% CI 0.35-0.79, p=0.002). A total of 689/892 (77 %) participants in the qualitative interview.  Almost all subjects (95.1 %) were aware that there was a test for COVID-19 diagnosis, with 83.3 % knowing about the availability of a vaccine. 

Conclusion: Our study reveals significantly lower vaccination rates among Vancouver's inner-city residents compared to the general population, which cannot be attributed to a lack of knowledge about COVID-19. Results from this study suggest that targeted, community-focused initiatives are crucial to address vaccine disparity among vulnerable populations living in Vancouver's inner city, particularly those facing unstable housing and injection drug use.

Background: Marginalized populations have lower vaccination uptake compared to the general population. Mobile low-threshold clinics play a crucial role in providing preventive care to these individuals who are disengaged from care, especially those actively using drugs, facing mental health and social challenges (including unstable housing) as well as other, more pressing, medical challenges. 

Methods: In this study, we implemented mobile community pop-up vaccine clinics, conducted in collaboration with housing societies in inner-city Vancouver. We conducted weekly mobile events at single-room occupancy dwellings. In the context of a broader offer of engagement in health care, we provided education about vaccination against respiratory infections, with nurses available to address specific questions about safety and efficacy. We then offered immunization for COVID-19, influenza and pneumonia to all who consented and or were eligible to receive them. 

Results: From October 2023 to April 2024, we held 34 events to engage 335 individuals in care. We administered a total of 527 vaccines, with 237, 221 and 69 influenza, COVID-19 and pneumovax immunizations. The 45% acceptance of influenza immunization is nearly identical to the rate achieved in the general population (44.4%). For COVID-19, this represented the first immunization in 15 individuals. A total of 125 individuals were already adequately vaccinated. A smaller number (69 doses) of pneumonia vaccines were given, as the majority of the target population was unfamiliar with this intervention and was reluctant to consent to its receipt at the time of first contact.

Conclusion: Lower vaccination rates among Vancouver's inner-city residents require targeted initiatives to provide low barrier access these important public health initiatives. Our mobile pop-up clinic program has ed to vaccination rates approaching those in the general population and will be expanded for the 2024-25 season to address the needs of this population in a more impactful way.

Flaviviruses continue to cause significant morbidity and mortality globally. ZIKV recently caused immense economic and health impacts throughout the Americas, and re-emergence poses a significant threat. Novel vaccine strategies for flaviviruses and Zika virus in particular, remain urgently needed. Here, we created a chimeric virus expressing ZIKV prM and E proteins on an Aripo virus (ARPV; an ISFV) backbone and assessed this vaccine candidate’s immunogenicity, efficacy and correlates of protection using in vitro and in vivo models. Our in vitro safety studies showed that after infection of mammalian cells with ARPV/ZIKV, the virus did not replicate nor cause cytopathic effects. ARPV/ZIKV did not produce ZIKV E protein in mammalian cells, and demonstrated exceptional safety when administered at high doses intracranially to suckling mice. Protective efficacy was next evaluated in immune -competent (C57BL/6J) and -compromised  (IFN-αβR^-/-) murine models. ARPV/ZIKV-vaccinated mice were completely protected from viremia, weight loss, and mortality after being challenged with ZIKV. ARPV/ZIKV immunization also prevented in utero ZIKV transmission in gravid IFN-αβR ^-/- mice. Vaccinated dams and their embryos exhibited no morbidity post-challenge, and no detectable ZIKV was present in placental, spleen, or brain tissues. Vaccine efficacy studies in Rag1^-/-, Tcra^-/-, and muMt^-/- mice, and T-cell depletion, adoptive transfer, and passive transfer studies in IFN-αβR^-/- mice, show both humoral and cell-mediated responses are important contributors to ARPV/ZIKV-induced protection. ARPV/ZIKV vaccination shows single-dose efficacy, and both neutralizing antibodies (nAbs) and T-cell responses mediate the robust protection observed, with nAbs playing a larger role at the time of challenge but T-cells playing a significant role in the development of protective immunity after ARPV/ZIKV vaccination in mice. Overall, ISFV vaccine platforms are being continually refined, and it seems plausible that they will be an important tool for reducing the global burden of flavivirus disease.

Introduction: Pneumococcal vaccinations play a crucial role in preventing pneumococcal infections. However, there is a concern regarding the persistence of vaccine-induced antibody titers. Italy's National Vaccination Schedule includes three doses of pneumococcal conjugate vaccine (PCV) administered during the first year of life. This study aims to assess the long-term persistence of pneumococcal antibodies.

Methods: We conducted a retrospective study analyzing pneumococcal antibody titers in fully vaccinated children with PCV13, aged one year and above (13 months to 18 years old), without underlying chronic conditions. Subjects were enrolled from January 2020 to December 2023 at Bambino Gesù Children Hospital (Clinical Immunology Unit and Infectious Disease Unit). Serological analysis was performed by the Microbiology and Diagnostic Immunology Unit. For the measurement of pneumococcal IgG titers,the VaccZyme™ anti-PCP IgG ELISA Kit (The Binding Site, Birmingham, United Kingdom) was used according to the manufacturer's instructions.

Results: Data from 241 children were analyzed, revealing that 48% displayed loss of specific pneumococcal antibody titers (Non Seroprotected - NS). No significant differences were observed between the NS and the Seroprotected (S) group in terms of gender, age and hematologic examinations (white blood-cells, neutrophils, lymphocytes, IgG and IgA levels). Moreover, participants underwent evaluation for specific antibody titers against Haemophilus Influenzae (HiB). Notably, 75% of NS group individuals exhibited protective titers against HiB. This finding was comparable in the S group (80%).

Conclusions: Our findings emphasize the need of monitoring pneumococcal antibody titers, particularly given the potential loss of serologic protection, which may pose heightened risks for individuals predisposed to invasive pneumococcal disease, such as those with underlying clinical conditions. Further investigation is warranted to elucidate factors contributing to waning vaccine-induced immunity and to establish the actual serological correlate of protection against pneumococcus.

Introduction: HPV infection is responsible for the majority of cases of cervical cancer, the 2nd most common and deadliest cancer in Africa. The HPV vaccine is available free of charge in the EPI, but coverage remains low. The aim of this study was to assess the knowledge, attitudes and practices of mothers of young girls aged 9 and over regarding HPV vaccination.

Materials and methods: Cross-sectional descriptive study, carried out from July 2023 to January 2024, and including mothers of 9-year-old girls, in the paediatric wards of the University Hospital Centers  of Treichville and Angre. Data were collected using an anonymous questionnaire.

Results: A total of 194 mothers were interviewed. Most had never heard of HPV infection (81.96%) and the HPV vaccine (63.40%). The main source of information for HPV infection was the media/internet (48.57%) and doctors/health workers (43.66%) for vaccination. None of the mothers had their child's vaccination record (or card) and 92.27% stated that their daughters had not been vaccinated against HPV and 7.73% that they had. The majority (94.3%) were in favour of vaccinating their daughters and 5.67% were against it, due to lack of information. Having heard about HPV infection and vaccination was significantly associated with vaccination (p<0,05). 

Conclusion: HPV vaccination could be improved by appropriate communication with the mothers of the vaccination recipients.

Background: In vitro systems based on human peripheral blood mononuclear cells (PBMCs) can bridge the gap between preclinical and clinical vaccine evaluation but have so far mainly been exploited to assess vaccine effects on antigen-presenting cells and T cells. Our study aimed to assess whether B cells present in PBMCs also respond to vaccines and reflect the effects of different vaccine formulations and adjuvants.

Methods: We stimulated PBMCs with whole inactivated virus (WIV) or split virus (SIV) H5N1 influenza vaccine, with or without the addition of the adjuvant cytosine phosphoguanine (CpG) ODN 2395, and collected the cells and supernatants at different timepoints. B cell subsets were measured by flow cytometry, immunoglobulin (IgG) levels by ELISA, B cell-related genes by qPCR, and cytokine levels by intracellular staining. 

Results: B cells in WIV-stimulated PBMC cultures differentiated more readily to plasmablasts and plasma cells and produced more IgG than SIV-stimulated cells. In line, PRDM1, XBP1, and AICDA, genes that promote the differentiation of B cells to antibody-secreting cells, were expressed at higher levels in WIV- than in SIV-stimulated PBMCs. The combination of WIV and CpG consistently induced the highest levels of antibody-secreting cell differentiation, IgG production, and B-cells secreting IL-6 and IL-10.

Conclusion: B cells in human PBMC cultures show distinct responses to the different types of vaccines and the CPG adjuvant regarding gene expression, cell phenotype distribution, IgG, and cytokine levels. This underlines the suitability of unfractionated PBMCs for evaluating vaccine effects on different types of human immune cells before running costly clinical trials.

Introduction: Compulsory vaccination of healthcare workers is intended to reduce the risk of contamination, and also of being a source of contamination, particularly for patients. The Covid-19 pandemic highlighted the refusal of healthcare workers to be vaccinated. The aim of this study was to investigate healthcare workers' perceptions of compulsory vaccination.

Materials and methods: A cross-sectional, analytical study at the National  Institute of Public Hygiene and the General Hospital of Port-Bouët, from January to March 2023, including all curative and preventive care staff.

Results: 390 people were interviewed. The study population was predominantly female (52.30%) with an average age of 38. Paramedical staff were in the majority (73.85%). The need to vaccinate healthcare staff was known by 64.61%, with prevention as the reason (95.64%). Yellow fever (58.20%) and Covid-19 (52.82%) were the vaccines for which most respondents were up to date. The majority of healthcare workers (88.72%) consented to compulsory vaccination. Fear of adverse effects was the most common reason for refusal (86.41%). Acceptance of compulsory vaccination was associated with having a vaccination record, and with socio-professional category, particularly being a doctor.

Conclusion: The persistence of obstacles to the vaccination of healthcare personnel calls for appropriate communication aimed at paramedical staff. In view of the emergence of diseases with epidemic potential, such as Covid-19 and Ebola, a law or regulation governing vaccination should be introduced.

Background: Negative issues are spreading among the public regarding the COVID-19 vaccine, so there are still people who are reluctant or afraid to be given the COVID-19 vaccine due to this wrong issue.

Objective: To know the reasons and factors that cause people to delay receiving the COVID-19 vaccination.

Method: This research is a descriptive study of Central Java, Indonesia's multi-site cities. Data were collected using an interview method and a questionnaire. 

Result:  In total, 537 subjects were involved in this study. The male was predominant,  357 (66,5%). Ninety-nine percent of the subjects were Muslim, and most of the subjects lived in rural areas. The questionnaire was divided into five questions: vaccine ingredients, side effects, lack of knowledge about vaccine/information constraints, and those unrelated to vaccines. There were 123 (22.9%) subjects worried about non-halal materials, and 122 (22,7%) feared side effects. Around 108 (20,1%) problems regarding non-vaccine, for example (transportation and availability), lack of understanding about the vaccine, 56 (10.4%), and 80 (16,0%) have no adequate information about vaccines. About 10 (1.9%) subjects had negative public issues regarding the COVID-19 vaccine and rejected the vaccination.

Conclusions: A special approach needs to be taken for people with a low socioeconomic level to have the correct view of the COVID-19 vaccine and be willing to be given it. Halal issues are still the most dominant variable in the reasons for delaying vaccines, followed by fears about side effects and non-vaccine obstacles in Indonesia.

Vaccination on COVID-19 plays important role on reducing the morbidity and mortality rate. The development of inactivated vaccine and addition of adjuvant such as aluminum salt and CpG has been expected to increase its safety and effectiveness. Therefore this study provide a SARS-CoV-2 Protein Subunit Recombinant Vaccine with Alum+CpG 1018. In this study, we were looked at the hematological trends. This study was an analysis of data from a Phase I study, Observer-Blind, Randomized, controlled on the Safety and Immunogenicity of SARS-CoV-2 Protein Subunit Recombinant Vaccine Adjuvanted with Alum+CpG 1018 in Healthy Population Aged 18 Years and over in Indonesia. The subject was divided into 5 groups, then the hematological profile will be compared from the baseline (before vaccination), 7 days after the first dose, and 14 days after the second dose. There was a decreasing pattern of red blood cells and neutrophils, decrease in leukocytes occurred only 7 days after the first dose, then increased again. The platelets levels were showed a variation in each group. There was an increase in eosinophils, monocytes, and lymphocytes. Changes in the hematological profile in this study were within normal limits.

Background: Migrants are considered a most vulnerable population group because of their unique positioning at the nexus of three global health threats namely climate change, conflict, and pandemics. Mobility increases migrants’ susceptibility to vaccine preventable diseases (VPDs) and limited access to health services. There is limited synthesized evidence on the systemic factors that determine whether migrant populations have fair and just access to routine childhood and adolescent immunisation services globally.  

Methods: We conducted a systematic scoping review using a Boolean search in 10 electronic databases. A total of 78 articles published between 2012 and 2023 were reviewed. An additional 11 grey literature documents sourced from global organisational websites were also included.

Results: Several countries reported having national immunisation programs (NIPs) guided by migrant inclusive policies, albeit with varied implementation. Generally, migrants had lower immunisation coverage and higher risk of VPDs compared to the general population. Though migrants are often described as homogenous populations, findings revealed several instances of exclusion of certain types of migrants from accessing immunisation services based on their legal status. Immunisation policies in home versus host countries are often not aligned, thus migrants may be inadvertently excluded from accessing immunisation services.

Discussion: Achieving global targets for the control and elimination of VPDs necessitates inclusion of migrants to improve their health and reduce the risk of importation of VPDs to host countries. More nuanced categorisation of migrants is needed to address the structural inequity evident in exclusion of certain categories of migrants from accessing preventive health services. Better synergy between home versus host country NIPs is critical in strengthening NIPs and ultimately, health systems for migrant-inclusiveness.

Conclusion: For migrant populations, access to immunisation services are a matter of social justice, necessitating inclusive policy reforms and strengthened collaborations across health systems in home and host countries.

The escalating climate crisis and habitat loss intensify the risk of spillover events. To bolster global pandemic preparedness, a diverse range of robust and reliable vaccine platforms is crucial. We present production, purification and immunogenicity of a novel vaccine candidate against Nipah virus, a high-risk pathogen with pandemic potential. We developed a multivalent Nipah virus-like particle (NiVLP) vaccine based on pathogen structural proteins. Employing sequential filtration and chromatography purification, we obtain highly pure and concentrated particles from insect cell culture. The purified nanoparticles are homogenous and form characteristic paramyxovirus morphology as observed with TEM. This methodology ensures dependable production scale-up for preclinical and clinical trials. The presented vaccine candidate induces robust immunity in a hamster model with or without squalene adjuvant. NiVLPs represent a safe and cost-effective vaccine platform ideally suited for global deployment. This is especially important in light of the increasing threat posed by emerging Nipah virus outbreaks.

Background:

The migrant population is considered to be an under-immunized group and thus at risk of vaccine-preventable diseases. So, identifying the specific challenges faced by newly arrived migrants (NAM) in accessing healthcare and vaccination services in first-line, transit and destination countries, as well as possible solutions and tools for increasing vaccination coverage, is of importance.

The study aimed to develop a country-specific action-oriented flowchart to overcome system barriers to the effective vaccination of NAM in Poland within the project “Access To Vaccination for Newly Arrived Migrants” (AcToVax4NAM).

Methods:

The study was based on the analysis of data from two online focus group discussions (FGDs) conducted in April 2024 with 19 stakeholders working with NAM in the field of immunization or the healthcare/social care sector.

Results:

Major themes concerned the: (1) NAM issues/characteristics: communication or language difficulties, low health/vaccine literacy and healthcare familiarity, (2) healthcare and context issues: lack of knowledge on the entitlement to health and vaccination for NAM, missed opportunities to vaccinate, ineffective outreach strategy, inadequate cultural competency and communication skills, lack of regularly collected and disseminated data about NAM.

Multi-sectoral policies, enhancing vaccine literacy, reinforcing immunization services and healthcare workers' skills, improving information systems for data collection and sharing, and increasing research and evidence production were some of the strategies proposed to enhance vaccination uptake among NAM and ensure “no one will be left behind”.

Conclusions:

Developing a Polish country-specific flowchart that identifies system barriers, strategies, and areas for improvement to ensure equitable access to vaccination for NAM is an important step towards achieving universal health coverage and health equity. Our findings highlight promising practices for increasing vaccine uptake and acceptance in place and further policies and actions to be implemented for the health of NAM to be protected in countries of transit and arrival.

Vaccine efficacy and duration of protective immunity, by determining T-cell function, should be systematically evaluated and monitored in the population. In Peru, different vaccination patterns have been received, highlighting the frequent use of BBIBP-CorV, an inactivated virus vaccine.The aim of the study was to evaluate the activation of T-cells against SARS-CoV-2 virus protein stimulation using a rapid quantitative PCR of the mCXCL10 gene amplification.Thirty-four participants were recruited in a cross-sectional study to assess their T-cell activation levels against SARS-CoV-2.A 1 ml of whole blood was collected, and was stimulated with spike peptides (covering the N-terminal S1 domain) from original Wuhan strain, and spike peptides from omicron BA.5 variant. Additionally, Phytohemagglutinin was performed as a stimulation control and media was used as a negative control. Total RNA extraction was performed for each group by Trizol method. Real-time quantification of mCXCL10 was performed, using the actin gene (as internal control). Characteristics of the volunteer population are shown table 1, thus, age mean 33.18 years, 35.3% was male, last COVID episodes 16.87+8.66 days, 41.2% had COVID before vaccination, volunteers received 3.47+0.74 vaccine doses and 41.2% included BBIBP-CorV.The t-cell activation values are higher in omicron stimulation than in spike (wuhan) 6.114+4.86 and 12+6.459 respectively. Significant differences have been found in sex, for both spike (wuhan) 8.17 vs. 4.98 for male and female (p=0.05) and omicron 16.51 vs. 9.54 (p=0.001) respectively. T-cell activation was significantly higher in vaccine patterns that do not include BBIBP-CorV 4.38 vs. 7.64 (p=0.049), but only in spike (wuhan). In multiple linear regression analysis sex was significantly associated with t-cell activation, for omicron [5.5-], males have on average 5.5 more than females, regardless of their age, the number of COVID episodes, the time of the last episode, the number of doses received and the months since the last vaccine dose.

Exposure to hemagglutinin from influenza A virus at an early life substantially contributes to the antibody response in adults, especially following natural influenza infection. In adults infected by contemporary seasonal influenza viruses, the circulating serum antibody responses showed strong patterns of reactivity to hemagglutinins from influenza A strains that circulated during a person’s childhood. This pattern was also reflected at the memory B cell level. Collectively, these observations suggest that seasonal influenza infection reinforces early-life imprinting and likely includes strong reactivity against the conserved hemagglutinin stem epitopes, therefore affording broad heterosubtypic anti-influenza protection. However, much less understood about the anti-influenza response generated during early life. Crucially, the breadth of anti-influenza specificities and magnitudes are not well-studied due to the limitations associated with collecting samples from infants. We performed comprehensive analyses on serum antibodies and hemagglutinin-reactive B cells in children under 12 months to 8 years old. We observed that hemagglutinin-reactive serum IgG and hemagglutinin-reactive memory B cells were generated from early-life exposure to hemagglutinin through inactivated influenza vaccination. Notably, the serum responses also included reactivities to the hemagglutinin stem epitopes in the vaccination cohort, suggesting that primary exposure via vaccination early in life does include anti-stem response, a pattern that is generally absent in adults. Collectively, our data suggests that influenza vaccination in children generated broad anti-hemagglutinin responses, which supports previous observations that memory B cells that were formed from this exposure could participate in future responses.

Background: Real-world COVID-19 with comorbidity and mortality-correlated factors at specialised care units of hospitals is scarce in Indonesia, and local evidence in each setting is crucial. This research aims to analyse the association between pre-existing comorbidity, vaccination, and COVID-19 mortality at specialised care unit admission of giant emergency hospital.

Methods: This retrospective cohort study included all isolated patients with pre-existing comorbidities (fourteen infectious and non-communicable diseases) at ICU, HCU, and IMCU admission at Wisma Atlet Hospital from March 2021 – December 2022 surveillance data. We extracted demographic, comorbidity, vaccination, and outcomes (recovered or deceased). We applied logistic regression to examine factors correlated with COVID-19 mortality.

Findings: Of 1516 isolated patients with comorbidities, 1103 (73%) recovered, and 413 (27%) died. The median age was 49 years (IQR 36-57), 29% had pulmonary comorbidities (asthma, COPD, tuberculosis, pneumonia, bronchitis), and 15% had >1 comorbidity. Additionally, 34% had been vaccinated, and 64% of the length of stay (LoS) was 8-14 days. 

Of those who had non-pulmonary-NCDs (obesity, cancer, stroke, hypertension, DM, hepatitis, kidney and heart disease), 32% (327/1032) died. In contrast, of those with pulmonary comorbidities, 15% died (66/433). Overall, 24% of those with only one comorbidity died, whereas 44% of those with >1 comorbidity died. However, 37% (185/508) of those vaccinated deceased; 39% (126/321) got second doses vaccinated. Of these, 95% proportion received Sinovac, and 4% were AstraZeneca. Deceased odds with comorbidity were associated with higher age, male sex, >1 comorbidity, >2 weeks of LoS, even vaccination. Across all comorbidities, the deceased odds were higher to those second doses of vaccination (aOR 2.03, 95% CI 1.51-2.73).

Conclusion: Overall, the mortality rate among patients was higher in NCDs (non-pulmonary) comorbidity and vaccinated. Even deaths occurred among those who had second doses of Sinovac. This vaccine is poorly effective in preventing death of COVID-19 within comorbidity.

Background:

In 2022, Poland was challenged with a large influx of Ukrainian migrants and war refugees, including the responsibility to take care of their health needs. Migrants, as an at-risk group, face vulnerability to vaccine-preventable diseases (VPDs) due to missed childhood vaccines and doses and marginalization from health systems in host countries.

This qualitative study aimed to explore the challenges healthcare providers (HCPs) face in delivering vaccinations to Ukrainian child migrants and refugees and the potential barriers they face in accessing vaccinations in Poland from the perspectives of doctors and nurses.

Methods:

The study was based on data analysis from 18 in-depth interviews with HCPs working with Ukrainian refugees conducted in Poland in 2023. We analyzed the data using the UNICEF Journey to Health & Immunization Framework.

Results:

The Journey to Health & Immunization framework presents two interrelated journeys  - one from the perspective of the Ukrainian mother and the other from the HCPs’ perspective. We identified three main topics: (1) communication difficulties (e.g., language barrier, poor communication skills, lack of tailored information sources), (2) health system barriers – unfamiliarity with the health system of the host country, missed opportunities to vaccinate, lack of medical history of the patient, and (3) contextual barriers such as low health literacy, lacking knowledge of the disease or its relationship to the vaccine, low perception of risk of disease or importance of vaccination.

Conclusions:

An essential aspect of providing health support for child migrants and war refugees in the host country is ensuring the continuity of immunization and addressing gaps in vaccination coverage in this vulnerable group. 

The study results can help authorities develop effective vaccine promotion strategies for this underimmunized group, ensure universal access to preventive services for them, and support HCPs in delivering the best possible care to those who need it.

In an unprecedented effort, a wide array of vaccines have been developed with remarkable speed in response to the coronavirus disease 2019 (COVID-19) pandemic. These first-generation vaccines helped mitigate the impact of the pandemic, but in order to reduce transmission rates and protect the more vulnerable and immunocompromised parts of the population, a next-generation of vaccines is necessary. Mucosal vaccines able to induce immunity in the respiratory tract could fill that role. The Newcastle disease virus (NDV) viral vector vaccine NDV-HXP-S was designed as a low-cost vaccine allowing self-sufficient production of COVID-19 vaccines in low- and middle-income countries. NDV-HXP-S can be grown in embryonated chicken eggs, which allows its production using the existing influenza vaccine manufacturing capacities. The vaccine virus was constructed to express the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike stabilized in its pre-fusion conformation. Here, we genetically engineered the NDV-HXP-S vaccine to match the SARS-CoV-2 variant of concern (VOC) XBB.1.5. One or two intranasal immunizations with NDV-HXP-S expressing the XBB.1.5 spike induced systemic and mucosal immunity in mice and protected them from challenge with the XBB.1.5 VOC. In addition, a single intranasal vaccination with NDV-HXP-S XBB.1.5 was sufficient to protect hamsters from XBB.1.5 infection. Furthermore, we demonstrated that virus shedding was significantly reduced in vaccinated hamsters, thereby preventing direct contact transmission to naive animals. Taken together, the data show that intranasal vaccination with variant adapted NDV-HXP-S induces protective mucosal immunity and reduces transmission rates in pre-clinical animal models.  

　The emergence of SARS-C0V-2 led to a global pandemic, but the emergence of a novel modality, mRNA vaccine, made it possible to prevent infection and severe disease. In a previous study, we showed that three doses of mRNA vaccine of the Wuhan strain increased not only the S-antibody titer but also the neutralizing antibody titre, and even the neutralizing antibody titer against the Omicron sub-variants increased, indicating that affinity maturation of antibody was promoted (Seki Y et a., Med. 2022; 3:406-421.e4.). However, the disadvantages of mRNA vaccines, such as low cross-reactivity with sub-variants and rapid waning of antibody titers, have been pointed out, and epidemic subvariant-specific vaccines such as BA.1 and BA.4-5 have now been additionally licensed. Recently, vaccination with the XBB.1.5 vaccine began in Japan in 2023, there are currently a variety of vaccination patterns, and it is unclear whether there are differences in antibody induction capacity and other characteristics depending on the combination of vaccines. 

     In this study, immunogenicity was evaluated using samples from healthcare workers from the 5th to 7th vaccination with BA.1, BA.4-5 and XBB.1.5 vaccines. The results of this study showed that the immunogenicity of the vaccine was not significantly different from that of the other vaccine combination. S-antibodies were induced in all vaccination groups compared to pre-vaccination levels, and neutralizing capacity against XBB.1.5 and recent endemic strain JN.1 was increased by vaccination with XBB.1.5 vaccine. The breakthrough infection group also had significantly higher S-antibody titers and neutralizing antibody titers, including mutant strains, than either of the vaccine-only groups. 

   We would like to present the different safety profiles such as cytokine changes observed with the different vaccination regimens at this congress.

Antimicrobial resistance is a growing global issue, mainly driven by the overuse and misuse of antibiotics. Streptococcus pneumoniae and Staphylococcus aureus are among the leading pathogens, often seen in secondary bacterial infections (SBIs) following influenza. Influenza infects up to 20% of the Northern Hemisphere population during winter, frequently causing epidemics. In Denmark, annual influenza vaccinations are offered to target groups to reduce hospitalisations and deaths. Previous models have focused on influenza transmission and mitigation through vaccination or antiviral medication, but few have explored the link between influenza and concurrent or subsequent bacterial infections.

This study examines the potential impact of modifying Denmark's influenza vaccine strategy on reducing hospitalisations, mortality, and antibiotic use associated with SBIs in patients with influenza. This study employs two models: one for influenza transmission and another for hospitalisations and deaths due to influenza and SBIs. Both models use ordinary differential equations and are primarily validated with Danish data. 

The influenza model results indicate a high infection burden in unvaccinated individuals aged 0-6 and 20-49 years, with 2,160 and 1,886 cases per 10,000 individuals, respectively. Among vaccinated individuals, the highest burden is in those aged 64 and older, with 828 cases per 10,000. Notably, the high burden in 20-49-year-olds is unusual compared to other studies. The SBI model estimates 3,726 hospitalisations from influenza-only infections and 584 from SBIs. Additionally, it estimates 271 deaths, with 28% attributed to SBIs. Among hospitalised patients, 3,116 (72%) receive antibiotics, but only 19% have an SBI.

Combining the two models demonstrates that alternative vaccination strategies can reduce SBI hospitalisations, deaths, and antibiotic use. The most effective strategies are vaccinating 79% of 50-64-year-olds or 50% of 7-19-year-olds, though these may be impractical due to various constraints. Consequently, vaccinating 30% of 7-19-year-olds could reduce SBI hospitalisations, deaths, and antibiotic use by 11-14%.

Background: Vaccination timeliness is not considered among standard performance indicators of routine vaccination programmes (i.e. vaccination coverage), yet quantifying delayed vaccinations could inform policies to promote in-time vaccination and design vaccination schedules. Here, we analysed vaccination timeliness for 24 routine childhood immunisations in 54 countries.

Methods: Individual vaccination status and timing were extracted from Demographic and Health Surveys, from 54 low- and middle-income countries for surveys conducted from 2010 onwards. Vaccination timing data was used to estimate age at vaccination for children <5, which was compared to recommended age of vaccination for each country and vaccine to determine delay. Vaccination delay evolution over time was described using estimates from different birth cohorts. To identify demographic-socioeconomic indicators associated with late vaccination, multivariable Cox regression models with country as a random effect were used to estimate Hazard Ratio for being vaccinated with each vaccine for each week post-recommended vaccination age.

Results: Vaccine coverage at their respective recommended age was highest for birth and first doses (e.g. BCG: 44%, DTP-D1: 18.9%) and lowest for later doses (e.g. DTP-D3: 7.4%, MCV-D2: 8.4%). Median delay was lowest for birth doses (e.g. BCG: 1-week (IQR: 0-4)), and it increased with later doses in vaccination courses (DTP-D1: 2 (0-4) weeks, DTP-D3: 4 (2-9) weeks). Although median delay for each vaccine dose remained largely constant over time, the range of delay estimates moderately decreased, especially for recently introduced vaccines (HepB, Hib, PCV, RV). Children living in rural areas had a lower vaccination uptake rate for birth doses but a higher rate of receiving doses scheduled at later ages than those living in urban areas.

Conclusions: Although vaccinations delays are generally low, there has been little improvement on routine timely immunisation over the last decade and children from deprived socioeconomic backgrounds are more likely to receive late vaccinations.

Background: Influenza virus and SARS-CoV-2 have different seasonality patterns, however vaccines co-administration could improve vaccination programs performance and attain better COVID-19 coverage.  

Objective: To assess PHH-1V safety and immunogenicity when co-administered with seasonal surface antigen, inactivated, squalene-based adjuvanted influenza vaccine (SIIV).

Methods:  HIPRA-HH-11 (EUCT: 2023-506189-29-00) is a phase II, randomized, double-blind, multi-centre trial in adults (>65 age) fully vaccinated against COVID-19. Participants were randomized 1:1:1, treated with: PHH-1V/Placebo, SIIV/Placebo or PHH-1V/SIIV, and followed up to day 28. Safety and tolerability of co-administered PHH-1V were assessed respect to each vaccine administered alone. Humoral immunogenicity was measured by changes in levels of neutralizing antibodies (PBNA) and by total antibody against RBD of the Spike protein of SARS-CoV-2 by ECLIA.

Results: At the cut-off date 181 participants were included. A total of 94 subjects (51.9%) reported at least one solicited AE; being 30 (48.4%) in SIIV arm, 26 (44.8%) in PHH-1V and 38 (62.3%) in co-administration. Pain at the injection site was the most frequently reported solicited AE. Other frequently reported solicited AE were local sensitivity, headache and fatigue.

PHH-1V alone or co-administered with SIIV induces an increase on neutralizing antibodies on against Omicron XBB.1.16 at day 28. Adjusted treatment GMT at base line and at day 28 were 390.1 and 1464.5 in the PHH-1V alone group and 328.8 and 1093.3 in the of PHH-1V co-administered, without a significative increase difference between the PHH-1V arms ( PHH-1V/PHH-1V+SIIV GMT ratio 1.34; p=0.716), but a significative difference was shown when compared to the SIIV alone arm (0.23; p< 0.0001). No significative differences were found for GMFR at day 28 between PHH-1V alone (3.73) or co-administration (3.40) with GMFR ratio of 1.11 (p=1.000).

Conclusion: Co-administration of two squalene-based adjuvated vaccines is safe and has no effect on PHH-1V immunity induction in ≥65 years old participants.

Background: Individuals with immunosuppressive conditions are at high risk of developing SARS-CoV-2–associated consequences and death, and their responses to vaccination widely vary upon the underlying immune impairment. PHH-1V is a recombinant vaccine based on a dimeric RBD of two SARS-CoV-2 variants, to boost immunogenicity in ³16. 

Objectives: To evaluate the immune response elicited by the PHH-1V booster vaccination in participants with 5 different types of immunosuppressive conditions.

Methods: HIPRA-HH4 study (NCT05303402) was a phase IIb/III, open label, single arm, multi-centre, trial. Participants with HIV and CD4 <400 cells/ml (PWH, n=61), Kidney transplant under ³ 3 immunosuppressive drugs (KTx, n=37), renal disease on chronic dialysis (HD, n=59), primary immunodeficiency on IgG substitution therapy (PAD, n=24) or autoimmune disease on anti-CD20 therapy (AID, n=57) with mRNA primary vaccination were included. 238 participants were enrolled, and humoral and cellular immune response at day 14 were measured by PBNA or VNA and, ELISpot and ICS assays against Omicron BA.1 and BA.2, as the dominant variant at inclusion.

Results: PHH-1V booster induced a significant increase in neutralizing antibody titres at day 14 compared to baseline against both variants in PWH, KTx and HD groups and a moderate increase on PAD, but no effect was observed on the AID group due to their complete B cell depletion. Significant increases in the frequency of IFNg T cells were also detected in the PWH, HD and PAD groups by ELISpot and/or ICS, that not reached statistically significance in the AID group. On the contrary, no increases were observed in the KTx group, which is consistent with their anti-rejection therapy.  

Conclusion: PHH-1V booster vaccination elicits both humoral and cellular immune response against SARS-CoV-2 on a broad range of individuals with immunosuppressive conditions. The response level varies according to the underlying condition and/or its associated treatment.

Mycobacterium tuberculosis remains the largest infectious cause of mortality worldwide, even with over a century of widespread administration of the only licensed tuberculosis (TB) vaccine, Bacillus Calmette-Guérin (BCG). mRNA technology remains an underexplored approach for combating chronic bacterial infections such as TB. We have developed a lipid nanoparticle (LNP)-mRNA vaccine encoding for a fusion protein of two immunogenic TB antigens, termed mRNA^CV2. In C57BL/6 mice intramuscularly vaccinated with mRNA^CV2, high frequencies of polyfunctional, antigen-specific Th1 CD4⁺ T cells were observed in the blood and lungs, which was associated with the rapid recruitment of both innate and adaptive immune cells to lymph nodes draining the site of immunisation. mRNA^CV2 vaccine provided significant pulmonary protection in M. tuberculosis-infected mice, reducing bacterial load and inflammatory infiltration in the lungs. Importantly, mRNA^CV2 could enhance immune responses and long-term protection when used to boost BCG-primed mice. These findings, which provide the first report of a highly protective LNP-mRNA vaccine for TB, highlight the potential of the LNP-mRNA platform for TB control and support further research to facilitate translation to humans.

Next-generation vaccines are required to address the evolving nature of SARS-CoV-2 and to protect against emerging pandemic threats from other coronaviruses. These vaccines should aim to elicit broad cross-protection, provide long-lasting immunity and facilitate equitable access for all populations. In this study, a panel of chimeric, full-length spike antigens were developed in stable CHO cells that incorporate mutations from previous, circulating and predicted SARS-CoV-2 variants. The lead candidate (CoVEXS5) was obtained from a high-yield production process with purity of >95%, long-term stability and elicitation of broadly cross-reactive neutralising antibodies when delivered to mice in a squalene emulsion adjuvant (Sepivac SWE™). In both mice and hamsters, CoVEXS5 immunisation reduced clinical disease signs, lung inflammation and organ viral titres after SARS-CoV-2 infection, including challenge with the highly immunoevasive Omicron XBB.1.5 subvariant. In mice previously primed with a licensed protein vaccine (NVX-CoV2373), CoVEXS5 could boost T cell immunity, as well as neutralising antibodies levels against viruses from three sarbecoviruses clades. The breadth of sarbecovirus cross-reactivity elicited by CoVEXS5 exceeded that observed after boosting with the NVX-CoV2373 vaccine. These findings highlight the potential of a chimeric spike antigen, formulated in an open-access adjuvant, as a next-generation vaccine candidate to enhance cross-protection against emerging sarbecoviruses in vaccinated populations globally.

The purpose of this initiative is to develop and deliver culturally appropriate and tailored child health education, including immunisation, to members of the Roma community. The initiative is a collaboration between the National Social Inclusion Office, the National Immunisation Office and Cairde, a health information and advocacy service, in Ireland. This initiative supports equitable access to universal child health services.

The sessions were planned with community representatives from Cairde. Two online education sessions were given, with 15 participants, facilitated by translators. Anonymous pre- and post-evaluation surveys were developed using standardised questions from the World Health Organisation ‘Behavioural and Social Drivers (BeSD) of Vaccination tool for achieving high uptake’. Qualitative questions on expectations and suggestions were analysed thematically. Survey results were analysed on Microsoft Excel. An evaluation meeting was planned and described narratively.

The pre-session survey response rate was 40% (n=6) and post-session survey response rate was 93% (n=14). After the session, there was an improvement in perceived importance of childhood vaccines (‘Thinking and Feeling domain’) with 44% increase in perception of vaccination as ‘very important’ (33% vs 82%). To assess ‘Social Process’, perception of family and friends choosing to vaccinate, improved by 50% (50% vs 100%). To assess ‘Motivation’, the decision to decline all vaccines improved from 50% to 0%. 

The results show that a community engagement initiative, may improve drivers of vaccination among Roma community members in Ireland. This collaboration is an opening for further dialogue and engagement for vaccine acceptance among the Roma community. Based on this initiative, and the findings from the evaluation, training of peer-support/community health workers nationally through a Roma Health Network education meeting is planned. Evaluation of these trainings will inform the co-development of tailored information and resources for use by health care professionals and peer support workers, working with the Roma community. 

The present work set out to evaluate the impact of ICTs in a investigation into the importance of vaccines. For this purpose, an activity was applied hybrid, that is, one part in person and the other remotely, using technological resources, then a class of students from a public school in the Federal District, seeking to analyze advances obtained in the teaching-learning process. Research was also carried out, with the objective of verifying the availability of these resources by students, as well as analyzing results after using technologies through the development of a didactic sequence addressing the topic of vaccines. The research data showed the students’ motivation for the use of technologies, providing greater engagement in the search for knowledge of biology and the topic of vaccines.

The current landscape of vaccine development is experiencing a surge in formulations incorporating novel adjuvants, presenting new opportunities to address previously unmet clinical needs. One such adjuvant, Chitosan (CS), has shown notable immune-stimulatory properties.However, a comprehensive understanding of its full potential as an adjuvant remains incomplete, necessitating systematic investigation and optimization. Our study aims to evaluate the adjuvant potential of CS in a recombinant SARS-CoV-2 vaccine.We systematically examine CS's in-vivo efficacy as a vaccine adjuvant in a murine model, methodically assessing key adjuvant characteristics throughout the experimental procedure.Our findings highlight CS's effectiveness in enhancing the immune response to the recombinant SARS-CoV-2 vaccine when administered intramuscularly. Mice vaccinated with the CS-adjuvanted vaccine exhibited significantly higher levels of antigen-specific antibodies compared to the non-adjuvanted group. These antibodies displayed high avidity, indicating a potential for improved efficacy. Additionally, CS orchestrated a balanced Th1/Th2 immune response, which is crucial for immunity against viral infections. A dose-response correlation was observed, with optimal efficacy at a dose of 50 µg CS with 5 µg recombinant protein. This suggests the potential for tailoring CS dosage to optimize vaccine efficacy. Moreover, CS exhibited an antigen dose-sparing effect.Mice vaccinated with a five-fold lower dose of antigen combined with CS showed comparable antibody responses and lymph node T-cell activation as those receiving the standard antigen dose. This finding holds significant implications for vaccine development, potentially allowing for reduced antigen content in vaccines, thereby increasing production capacity and lowering costs.The immune-enhancing properties of CS may be attributed to its ability to recruit innate immune cells, especially neutrophils and macrophages, to the injection site. Furthermore, our findings indicate a long-lasting depot effect of chitosan for up to seven days at the injection site. This sustained antigen release ensures prolonged exposure to the immune system, potentially contributing to the robust immune response observed.

Virus-Like Particles (VLPs) are viral protein structures widely used as adjuvants for the formulation of new vaccines. The adjuvant properties of VLPs are associated with the stimulation of the innate immune response, which subsequently contributes to the activation of the specific immune response, mainly cellular immunity mediated by CD4+ and CD8+ T cells. In this work, we used recombinant VLPs from Triatoma virus as a vaccine adjuvant (Queiroz et al., Vaccine, 39, 2021) and three VLP structural proteins, called VP1, VP2 and VP3. Then, an experimental immunization model (Balb-C mice) was used to evaluate the ability of VLPs and structural proteins (VP1, VP2 and VP3) to induce different types of IgG antibodies, when associated with native or recombinant antigens of Trypanosoma cruzi or Leishmania amazonensis, protozoa responsible for Chagas disease and leishmaniasis, respectively. Our data show the ability of these vaccine adjuvants to preferentially induce IgG2a and IgG3 type antibodies, when compared to IgG1 antibodies. Therefore, these adjuvants, based on VLP vaccines, can be an interesting strategy to explore the immunoregulation process during vaccine development, especially when the aim is to polarize the induction of the immune response towards the humoral or cellular pathway, an important condition in the control of infections caused by some protozoa.

Background

Bovine mastitis remains a major challenge for dairy farming causing a pronounced reduction in milk production and quality. Mastitis can be caused by different pathogens, but among these Staphylococcus aureus (S. aureus) stands out, being considered the most prevalent. Also, is considered a pathogen of great importance for food safety and public health, due to its high pathogenicity, high transmission capacity, and resistance to antimicrobial treatments. The best strategy for controlling a pathogen with these characteristics is the development of an effective vaccine. Our group previously identified S. aureus’ candidate antigens using serum immunoproteomics. Recently, we evaluated different vaccination protocols and observed the induction of type 3 immunity, suggesting the development of protective immune response against S. aureus. The aim of the present work is to develop of a new mRNA vaccine for S. aureus-induced mastitis.

Materials and methods

We tested different prototypes of Nano-emulsion (NE)-mRNA formulations, coding for 3 different antigens, in vitro. Human alveolar basal epithelial cells (A549), and mouse macrophages (RAW 264.7), were transfected with NE-mRNA formulations. Transfection efficiency was assessed by measuring the percentage of transfected cells. The cytotoxicity of the formulations was evaluated using AlamarBlue, and by 7-AAD viability staining.

Results

In vitro preliminary data using NE-mRNA formulations indicate that formulations can efficiently deliver mRNA and induce expression of the encoded antigens in different cell types, with low cytotoxicity.

Conclusions

The NE-mRNA technology presented here is safe and can efficiently deliver mRNA to various cell types. Selected NE-mRNA formulations will be tested as new vaccine candidates against S. aureus-induced mastitis in a mouse model of S. aureus infection to evaluate safety, immunogenicity, and efficacy.  

Background: Surveillance systems for monitoring and reporting adverse events following immunisation (AEFI) and adverse events of special interest (AESI) are vital in understanding safety profiles of marketed vaccines. Evaluation of surveillance systems is necessary for systems strengthening. We aimed to conduct the first evaluation of the South African AEFI surveillance system, since inception in 1998.  

Methods: Using CDC guidelines, we conducted a cross-sectional evaluation of system attributes, through quantitative analysis of AEFI/AESI data since the COVID-19 vaccine rollout (17/02/2021) and semi-structured interviews with AEFI surveillance personnel. Findings were contextualized through examination of similar systems globally, offering insights into enhancing AEFI surveillance efforts.

Results: The system collects and manages AEFI data, employs investigative tools and has an established AEFI committee conducting causality assessment, thus meeting WHO minimal capacity for vaccine safety. System adaptation through inclusion of digital applications (MedSafety) facilitated public reporting, whilst increasing complexity of database management. Respondents demonstrated engagement with the system through accounts of their roles in AEFI surveillance. Between 17/02/2021 and 31/12/2022, 38,271,716 doses (BNT162b2 and Ad26.COV2.S) were administered, and 3942 AEFI reported (reporting rate: 10.3/100,000 doses). AEFI reporting rates varied considerably across provinces, ranging from 1.5 to 52.7 AEFI/100,000 doses. By 31/12/2022, 25% of serious and severe cases were causality assessed. 

Conclusion: We observed a functional, useful, flexible system with high reported stakeholder and public acceptability levels. Challenges identified included low reporting rates from some provinces, weak co-ordination between manual and application-based reporting and resource limitations. Shifting pharmacovigilance perception is critical in ensuring decision-makers understand its vital role in vaccine safety. Harmonization of passive surveillance reporting systems would enhance signal detection and eliminate data duplication. Globally observed active digital surveillance allows efficient data collection and automated triage of cases for prioritization. Evaluation of provincial and district components could ensure comprehensive system development across all levels.

Though widely applied in other epidemiological fields, the case-cohort study design has seen little application in the field of vaccinology.  Case-cohort studies use probabilistic sampling and reweighting to draw inferences about effects (in this case vaccine efficacy) at the population level in an efficient manner.  The SARS-CoV-2 pandemic was met with high vaccine uptake, and high rates of population testing prior to the emergence of Omicron variants of concern, in Ontario, Canada, providing an ideal environment for application of case-cohort methodology.  We combined a population-based case line list and vaccination database for the province of Ontario between December 2020 and October 2021. Risk of infection after vaccination was evaluated in all laboratory-confirmed vaccinated SARS-CoV-2 cases, and a 2% sample of vaccinated controls, evaluated using survival analytic methods, including construction of Cox proportional hazards models.  Vaccination status was treated as a time-varying covariate.  First and second doses of SARS-CoV-2 vaccine markedly reduced risk of infection (first dose efficacy 68%, 95% CI 67% to 69%; second dose efficacy 88%, 95% CI 87 to 88%).  In multivariable models, extended dosing intervals were associated with lowest risk of breakthrough infection (HR for redosing 0.64 (95% CI 0.61 to 0.67) at 6-8 weeks).  Heterologous vaccine schedules that mixed viral vector vaccine first doses with mRNA second doses were significantly more effective than mRNA only vaccines.  Risk of infection largely vanished during the time period 4-6 months after the second vaccine dose, but rose markedly thereafter.  We conclude that a case-cohort design provided an efficient means to identify strong protective effects associated with SARS-CoV-2 vaccination in real time, and also served to quantify the timing and magnitude of infection breakthrough risk in the same cohort.  Heterologous vaccination and extended dosing intervals improved the durability of immune response.

Background: Individuals with immunosuppressive conditions are at high risk of developing SARS-CoV-2–associated consequences and death. PHH-1V is a recombinant vaccine based on a dimeric RBD of two SARS-CoV-2 variants, authorised to boost immunogenicity against SARCoV-2 in vaccinated adults.

Objectives: To evaluate the safety and reactogenicity profile of PHH-1V as booster vaccine in participants with 5 different types of immunosuppressive conditions.

Methods: HIPRA-HH4 study (NCT05303402) was a phase IIb/III, open label, single arm, multi-centre, trial. Participants with HIV and CD4 <400 cels/ml (PWH, n=61), Kidney transplant under ³ 3 immunosuppressive drugs (KTx, n=37), renal disease on chronic dialysis (HD, n=59), primary immunodeficiency on IgG substitution therapy (PAD, n=24) or autoimmune disease on anti-CD20 therapy (AID, n=57) with mRNA primary vaccination were included. Solicited adverse events (AE) were collected for 7 days after vaccination. COVID-19 episodes and safety were collected over 1 year of follow-up.

Results: 238 participants were included on the safety population, mean age of 56, with comorbidities and significant degree of immunosuppression. 225 participants ended the study (95% retention). There were 4 voluntary withdrawals (1,68%), 1 loss due to an adverse event, 1 lost of follow-up and 7 deaths. None of the withdrawals or deaths were deemed to be related to the vaccination. 

580 solicited AE in 165 (69%) participants. Most solicited AE were Grade 1 or 2, being pain at injection site, fatigue and headache the most frequent. There was a total of 82 severe adverse events (SAE) in 57 (24%) participants, none of them related to PHH-1V. 70 (29%) participants reported confirmed COVID-19, of which, 5 required hospitalization (1 at ICU). No-COVID-19 related deaths.

Conclusion: PHH-1V was safe and well tolerated in individuals with pre-existing immunosuppressive conditions. Levels of SAE and severe cases of COVID-19 were consistent with a population with high burden of comorbidities.