Human Vaccines & Immunotherapeutics

Background: COVID-19 vaccination uptake is influenced by various sociodemographic and psychological factors. Previous studies have suggested that the relationship between personality traits and vaccination is context-dependent. However, this association has not been investigated in Japan, a unique sociocultural context characterized by historically low vaccine confidence but exceptionally high COVID-19 vaccine uptake. We examined the association between the Big Five personality traits and completion of the primary COVID-19 vaccination series, exploring potential gender-personality interactions. Methods: A web-based, cross-sectional survey was conducted among 7,210 Japanese adults (aged 20-85 years) in December 2021. Personality was assessed using the Japanese version of the Ten-Item Personality Inventory. Multivariable Poisson generalized estimating equations were used to calculate adjusted prevalence ratios (PRs) and assess gender-personality interactions. Results: Higher extraversion and lower openness were significantly associated with vaccination completion across genders. A significant gender-agreeableness interaction was observed: agreeableness (PR = 1.016, 95% CI: 1.008-1.024) was positively associated with vaccination completion among men but not women. A similar, though only marginally significant, interaction pattern was observed for neuroticism (PR = 1.011, 95% CI: 1.004-1.019 among men). Conclusions: Personality traits act as modest but meaningful, gender-specific psychological modifiers of vaccination behavior in Japan. Public health campaigns should transition from traditional "one-size-fits-all" messages to personality-tailored and gender-responsive communication strategies to optimize vaccine uptake and bolster psychological resilience in future pandemics.

Respiratory infections remain a relevant global health concern nowadays. The rapid dissemination and high mutational ratio of some pathogens, amid human demographic drivers, increases their pandemic potential. On the other hand, some bacterial infections have re-emerged with new resistant variants, supporting the need of updated or more potent vaccines. The development of nasal vaccines, with the capacity to efficiently induce immune response at the respiratory tract and systemic compartments, constitutes an appealing strategy to tackle respiratory infections, including tuberculosis. In this work, two synthetic compounds, the ODN-39M and the peptide LALF32-51, are evaluated as nasal vaccine adjuvants for the Ag85B antigen from Mycobacterium tuberculosis. The capacity of such adjuvants to enhance the immune response at systemic and mucosal compartments following intranasal immunization was assessed in Balb/C mice. The ODN-39M was able to potentiate the immune response, showing preferentially a Th1 pattern. The vaccine preparation containing this CpG adjuvant plus Ag85B induces potent cell-mediated and high IgA specific antibody response in lungs, along with systemic immunity. A preliminary study of the interaction between the ODN-39M with the NALT immune cells shows the early recruitment of lymphoid cells, and the increase of CD69 activation marker, mainly in B and dendritic cells. Although further studies should be done to reach a deeper understanding of NALT functioning, including the development of local innate response, the current data enrich the scarce reports focused on this compartment and support the use of the ODN-39M as a potent and potentially safe adjuvant option for future nasal vaccines.

Aims: To estimate the preventable pneumococcal disease burden by 21-valent pneumococcal conjugate vaccine (PCV21) compared to PCV20 for the national immunization program for adults aged 65 years or older in Japan. Methods: Serotype distribution among isolates and the annual incidence of invasive pneumococcal disease (IPD) in adults were monitored. The numbers of IPD or pneumococcal community-acquired pneumonia (pCAP) cases preventable by immunization with PCV20 or PCV21 were estimated according to reported vaccine efficacy and duration of protection in older adults. Data from our nationwide study of adult IPD surveillance and a multicenter study of pCAP were used. Results: The mean annual incidence of adult patients with IPD caused by all serotypes among adults aged [≥]65 years, which declined during the COVID-19 pandemic period, recovered to 89% of the pre-pandemic level in 2025. During 2023-2025, the proportion of PCV20-non-PCV21 serotypes was 8.5% for adults aged [≥]65 years. At the current vaccination coverage rate of 40%, the numbers of preventable IPD cases (per person per year) by PCV20 and PCV21 were 36 and 53, respectively. The preventable numbers of pCAP cases by PCV20 and PCV21 were 2,821 and 4,765, respectively. The estimated number of preventable pCAP cases was approximately 80-90 times higher than that of preventable IPD cases. Conclusion: Our data indicate that PCV21 could prevent 1.5-1.7 times as many pneumococcal disease cases as PCV20 among adults aged [≥] 65 years in Japan. However, PCV20 should be considered if the incidence of adult IPD cases caused by PCV20-non-PCV21 serotypes increases.

Objective: This study estimated the vaccine effectiveness (VE) of 20-valent pneumococcal conjugate vaccine (PCV20) against culture-confirmed pneumococcal pneumonia hospitalizations among adults using a test-negative case-control design. Methods: We included adults ([≥]18 years) hospitalized with pneumonia in the U.S. Veterans Affairs Healthcare System between January 2023 and December 2025 who had respiratory cultures collected. VE was estimated using multivariable logistic regression adjusted for demographic and clinical characteristics. Subgroup analyses were conducted by age, risk group, and U.S. census region. Sensitivity analyses included inverse probability of treatment weighting (IPTW) and evaluation allowing previous PCV13 vaccination. Results: Among 34,009 pneumonia hospitalizations, 837 (2.5%) were Streptococcus pneumoniae culture-positive and 7,428 (21.8%) individuals had received PCV20. PCV20 vaccination was associated with lower odds of culture-confirmed pneumococcal pneumonia hospitalization among adults aged [≥]65 years (VE 20.4%; 95% CI: 2.1%, 35.3%), with greater effectiveness observed among those with chronic medical conditions (VE 24.4%; 95% CI: 0.7%, 42.4%). VE was highest in the Western region among adults aged [≥]65 years (39.6%; 95% CI: 3.2%, 62.3%), a region with a high burden of serotype 4 disease. Overall, VE among adults aged [≥]18 years was 8.8% (95% CI: -8.8%, 23.6%). Findings were consistent across multivariable and IPTW-adjusted analyses. Conclusion: PCV20 provided significant protection against pneumococcal pneumonia hospitalizations among older adults, with greater effectiveness in regions where vaccine-covered serotypes are more prevalent. These findings support the importance of aligning pneumococcal vaccination strategies with regional serotype distribution to maximize vaccine impact.

Objectives To evaluate the impact of COVID-19 vaccination on the prevention of long COVID (LC) in the Omicron era through an updated systematic review and meta-analysis. Methods We performed an update of our previously published systematic review and meta-analysis of vaccination and LC risk (searches between 1 January 2022 and 1 March 2024). Databases (Embase, MEDLINE, PubMed, Europe PMC, LILACS, Cochrane COVID-19 Study Register) were searched for studies published between 1 March 2024 and 13 July 2026. Observational studies assessing the impact of vaccination on the risk of LC four or more weeks after SARS-CoV-2 infection were included. Vaccines were restricted to those centrally authorised in the European Union. Random-effects meta-analyses, restricted to adults, were performed to calculate pooled odds ratios (OR) of LC in three comparisons: vaccinated (any dose) versus unvaccinated; booster vaccination versus unvaccinated; and booster vaccination versus primary course vaccination only. Results Nineteen new studies were identified, of which ten were included in the updated meta-analyses alongside eight studies from the original review. The pooled OR of LC in vaccinated adults (any dose) versus unvaccinated was 0.75 (95% confidence interval [CI] 0.67-0.84; 13 studies). ORs were also lower for booster vaccination versus unvaccinated (0.73; 95% CI 0.65-0.82; 6 studies), and booster vaccination versus primary course vaccination (0.63; 95% CI 0.53-0.75; 6 studies). Significant associations between vaccination and lower LC odds were observed in subgroup analyses of mRNA-only vaccination and LC outcomes three or more months after infection. Conclusions This updated review and meta-analysis reinforces our previous finding that vaccination may reduce the burden of LC in the Omicron era, with booster doses potentially providing additional protection. Although evidence in high-risk groups now prioritised for vaccination in most countries remains limited, these findings clearly demonstrate the benefits of vaccination and support current seasonal vaccination strategies.

There are currently no approved vaccines or medical countermeasures for use in prevention or treatment of Bundibugyo virus disease. A critical question is whether the existing vaccines approved for use against Ebola virus disease could provide sufficient cross-reactivity and cross-protection against Bundibugyo virus disease. We performed a systematic review and meta-analysis of published studies of antibody cross-reactivity to Bundibugyo virus (BDBV) after vaccination with previously approved Ebola vaccines (Ervebo or Zabdeno/Mvabea). We find on average a 2.8-fold (95% predictive interval, PI: 2.6-3.0) drop in binding (n = 8 observations from 4 studies) and 3.1-fold drop (95% PI: 2.0-4.8) in neutralization (n = 2 observations from 1 study) between Ebola virus and BDBV antigens after Ervebo vaccination, which appears maintained over time after vaccination. Very limited data on cross reactivity after Zabdeno/Mvabea vaccination suggests a higher drop in recognition of BDBV (39.7-fold, 95% PI: 24.8-63.8; n = 3 observations from 2 studies). In addition to analysis of antibody recognition in humans, we also investigated evidence for vaccine protection from BDBV challenge in animal models after Ervebo or other recombinant vesicular stomatitis virus (rVSV) based vaccines containing only Ebola antigen. A single study in NHP showed non-significant vaccine protection from BDBV challenge, while a study in ferrets showed significant protection after both one and two doses. The available data demonstrate immune cross-reactivity and some evidence for protection in animals, although further clinical and pre-clinical data is urgently needed to inform decisions on the use of Ervebo to protect against Bundibugyo virus disease.

We compared the immunogenicity of three licensed egg-based inactivated influenza vaccines, including TetrAnflu (Sinovac quadrivalent), Fluarix Tetra (GSK quadrivalent), and Vaxigrip (Sanofi trivalent), in adult healthcare workers in Hong Kong during the 2025/26 season. Paired pre- and post-vaccination sera from age- and sex-matched recipients (n=30 to 40 per group) were tested by hemagglutination-inhibition assays against vaccine strains. After adjustment for age, sex, and sampling interval, the vaccines induced broadly comparable rises in antibody titers, proportions achieving titers >=40, and seroconversion rates, with a superior response to A(H1N1) after TetrAnflu. These real-world findings support the interchangeability of these vaccines for influenza vaccination programs.

Bacille Calmette-Guerin (BCG) remains the only licensed tuberculosis (TB) vaccine, yet its protective efficacy against adult pulmonary TB is limited. To overcome this, we evaluated a novel recombinant Mycobacterium smegmatis (rMs) booster vaccine expressing Ag85B and ESAT-6 via the pMyong2 vector, combined with oat-derived {beta}-glucan adjuvant, to enhance BCG-primed immunity. BALB/c mice were primed with BCG and boosted twice with homologous BCG or varying doses of rMs with or without {beta}-glucan. Five weeks post-booster, mice were challenged intraperitoneally with M. tuberculosis H37Ra. Systemic bacterial clearance in liver tissue, cell-mediated immunity IFN-{gamma}, IL-17a, and antibody responses IgG, IgG2c, IgA were evaluated 3 weeks post-challenge. All rMs booster groups (rMs, high-dose rMs H, low-dose with {beta}-glucan, rMs {beta}) achieved complete systemic clearance of H37Ra with no detectable CFUs (colony forming unit), significantly outperforming mock-vaccinated and repeated BCG groups (**p < 0.01). Repeated BCG revaccination showed higher bacterial loads than single BCG (***p < 0.001), confirming no booster effect. Low-dose rMs with {beta}-glucan maintained 100% survival and total bacterial elimination despite a 50% dose reduction. Immune markers did not strictly correlate with clearance. Homologous BCG revaccination provides no additive protection, whereas pMyong2-based rMs confers robust systemic bacterial clearance. Adjuvanting with {beta}-glucan enables dose reduction while preserving maximum efficacy, establishing rMs as a promising heterologous TB booster candidate.

Background: Vaccination of people with HIV (PWH) on suppressive antiretroviral therapy (ART) represents a novel approach for evaluating candidate broadly neutralizing antibody (bnAb) immunogens for preventive and therapeutic HIV vaccines. Given pre-existing immunity in PWH, the safety of this approach requires careful assessment prior to broader application. Here, we report on the design and safety of the RENEW-SHCS study which evaluates the immunization of PWH with BG505 SOSIP.v4.1-GT1.1, an immunogen engineered to induce precursors of CD4 binding site (CD4bs)- and V2-apex targeting bnAbs. Methods. RENEW-SHCS is a phase I, open-label, non-randomized vaccination trial evaluating a single dose of the recombinant germline-targeting envelope trimer BG505 SOSIP.v4.1-GT1.1 (GT1.1), adjuvanted with 3M052-AF and Aluminum hydroxide (alum), in PWH on suppressive ART enrolled from the Swiss HIV Cohort Study. Participants were previously classified as bnAb or non-neutralizing antibody (nnAb) inducers, with a target enrollment of 15 per group, and were monitored for safety and immunogenicity for 24 weeks while continuing standard ART. Due to an out-of-specification stability measurement of adjuvant 3M052-AF the trial was paused after 23 immunizations and subjected to an unscheduled interim safety and reactogenicity assessment comprising protocol defined outcome measures (adverse events, clinical laboratory measurements and HIV-1 viral load). Results. Twenty-three participants (10 bnAb and 13 nnAb inducers, median age 59 years, 17 male / 6 female) were vaccinated between March and August 2025 before interruption of the trial. All participants completed follow-up with full protocol adherence. The interim-safety analysis confirmed that no vaccine-related serious adverse events occurred. Solicited local (96%) and systemic (83%) reactions were common, predominantly grade 1-2, transient, and self-limited. Transient laboratory changes occurred but mostly remained within the normal range, with no vaccine-related grade 3 abnormalities. We observed predominantly transient local and systemic reactions, which were similar or milder to the reactogenicity profile reported for immunization of adult people without HIV (PWOH) with GT1.1 adjuvanted with AS01b reported in the IAVI C101 trial. No viral rebound under ART occurred. One participant experienced two viral blips (>50 HIV-1 RNA copies/ml), one before and one 16 weeks after vaccination with subsequent re-suppression. All others maintained viral suppression (<50 copies/ml) throughout follow-up. Conclusion. RENEW-SHCS demonstrated a favorable safety and reactogenicity profile of single dose immunization with GT1.1 in PWH, comparable to that observed in PWOH. The findings of this phase I study support the feasibility of vaccinating ART-treated PWH in trials of preventive and therapeutic HIV vaccine strategies.

Staphylococcus aureus (S. aureus) is a major human pathogen that causes a wide range of superficial skin infections to the life-threatening systemic diseases. Emergence and increasing prevalence of anti-biotic resistance S. aureus strains have accelerated the need for effective vaccines. As S. aureus pathogenesis involve its surface antigens to facilitate the colonization and invasion into host, targeting these surface antigens represent a promising strategy for S. aureus vaccine development. In this study, we evaluated the efficacy of two surface antigens of S. aureus -fibronectin-binding protein A (FnBPA) and lipoteichoic acid (LTA) as vaccine candidates. We have generated a recombinant fusion protein r-FR by fusing the N-terminal region of FnBPA and rhizavidin and expressed in Escherichia coli. The recombinant protein was mixed with the biotinylated LTA to generate r-FR+LTA antigen mixture, emulsified with Freunds adjuvant as r-FR+LTA antigen mixture or r-FR alone and immunized to BALB/c mice. Mice immunized with r-FR+LTA mixture displayed a strong antibody response, strong bacterial growth inhibition in vitro and increased survival following lethal S. aureus challenge compared with mice immunized with r-FR alone. These findings suggest that incorporation of the S. aureus surface antigens like FnBPA with LTA provides improved protective efficacy and highlights the potential of a multi-antigen vaccine strategy for preventing S. aureus infections.

BACKGROUND Current polio vaccines face challenges including vaccine-derived poliovirus and high-containment manufacturing. We evaluated a recombinant trivalent virus-like particle (VLP)-based poliovirus vaccine (VPV) for safety and immunogenicity in a first-in-human phase 1 trial. METHODS In this randomized, observer-blind, active-controlled trial, 72 healthy adults (18 to 54 years) were assigned (1:1:1:1) to receive a single dose of VPV at low (45:8:25 D-antigen units [DU] + 0.1 mg aluminum phosphate [AP]), medium (45:8:25 DU + 0.3 mg AP), or high (90:12:45 DU + 0.3 mg AP) doses, or conventional inactivated poliovirus vaccine (cIPV). Primary outcomes were safety and tolerability. Secondary outcomes included neutralizing antibody titers through day 180. RESULTS No serious adverse events or Grade 3 reactions were reported. Solicited adverse events were reported in 77.8%, 55.6%, and 72.2% of the low-, medium-, and high-dose VPV groups, respectively, and 66.7% in the cIPV group. By day 29, VPV induced dose-dependent neutralizing antibody responses. For serotypes 1 and 2, the high-dose VPV group achieved geometric mean titers (GMTs) of 73,582 (95% CI, 31,198-173,545) and 110,623 (95% CI, 59,276-206,451), respectively, comparable to cIPV at 45,161 (95% CI, 20,973-97,244) and 112,361 (95% CI, 58,280-216,625). Although serotype 3 GMTs were lower for the high-dose VPV at 18,905 (95% CI, 8737-40,906) than for cIPV at 61,431 (95% CI, 31,123-121,251), 100% of high-dose VPV recipients achieved neutralizing titers [&ge;]1:1024. CONCLUSIONS A single dose of VPV was safe and highly immunogenic, supporting its potential as a next-generation vaccine to advance global polio eradication. (Funded by the Gates Foundation and Tianjin Leading Enterprises Innovative project 23YDLQSY00100; ClinicalTrials.gov number, NCT06101173).

Introduction Hepatitis E virus (HEV) in pregnancy is associated with high maternal and perinatal morbidity and mortality. The safety and efficacy of the recombinant protein HEV vaccine (HEV239, Hecolin) have been established in non-pregnant adult populations but there is limited information among pregnant women. This trial has two co-primary objectives: 1) to assess pregnancy-related and/or serious safety events among pregnant women between 14 and 34 weeks of gestation receiving two Hecolin doses four weeks apart compared to placebo recipients, and 2) to determine immune non-inferiority of pregnant recipients of two Hecolin doses four weeks apart compared to non-pregnant women. Methods and Analysis This is a multi-site, randomized, observer-blinded, placebo-controlled vaccine safety and immunogenicity trial in pregnant women and non-pregnant women of reproductive age in Karachi, Pakistan. A total of 2,358 healthy women will be enrolled, including 2,208 pregnant women between 14 and 34 weeks of gestation, who will be randomized in a 1:1 ratio (stratified by gestational age, 14-27 and 28-34 weeks) to receive either Hecolin or a normal saline placebo in two doses administered 1 month apart during pregnancy and a third dose administered postpartum, approximately 5 months after the second dose. A third arm of 150 non-pregnant women aged 16-45 years will receive Hecolin on 0, 1, and 6 months. The co-primary outcomes will be (i) the proportion of pregnancy-related AESIs and SAEs in pregnant participants from the first dose until the end of study follow-up, compared with placebo, and (ii) the geometric mean concentration (GMC) of anti-HEV IgG at four weeks after the second dose, comparing pregnant vaccine recipients with non-pregnant vaccine recipients (non-inferiority margin of 0.67 for the GMC ratio). Immunogenicity will be evaluated in a pre-specified subset of 300 participants receiving Hecolin, including 150 pregnant participants and 150 non-pregnant participants. Secondary outcomes will include maternal, neonatal, and infant safety outcomes, as well as immunogenicity according to the number of Hecolin doses received and the trimester of vaccination. Ethics and Dissemination The trial was approved by the National Bioethics Committee (NBC) of Pakistan (Reference number: 4-87/NBC-910), the institutional Ethics Review Committee (ERC) of the Aga Khan University (Reference number: 8298), and the Institutional Review Board (IRB) of the International Vaccine Institute (IVI) (Reference number: 2022-007). All participants will provide written informed consent in accordance with Good Clinical Practice. The results will be submitted to World Health Organization (WHO) Strategic Advisory Group of Experts in Immunization (SAGE), and disseminated through conference presentations, and peer-reviewed publications.

Objectives: Cervical cancer is Cameroon's second most common cancer among women. However, high parental Human papillomavirus (HPV) vaccine hesitancy impedes elimination, and no validated predictive tool exists. This study aimed to develop and internally validate machine learning models predicting parental HPV vaccine hesitancy in the Buea Health District and identify key predictors. Methods: This secondary analysis used cross-sectional survey data from 1,156 parents of children aged 9-18 years. Hesitancy was derived from self-reported vaccination status and intention. Twenty-six predictor groups were screened via group LASSO (17 retained for logistic regression; all 26 for tree-based models). Data were split 80/20 into training (n=925) and test (n=231) sets. Logistic regression, random forest, and XGBoost were tuned via repeated cross-validation while thresholds were set by Youden's J statistic. Discrimination, calibration, and Brier score were assessed on the test set. Predictions were interpreted using SHAP. Results: All models showed comparable discrimination (AUC-ROC 0.841-0.870). XGBoost had the highest AUC (0.870, vs 0.869 for logistic regression, DeLong p=0.965); logistic regression had the highest sensitivity (73.1%), F1-score (74.9%), and lowest Brier score (0.1435). Calibration slopes exceeded 1 (1.12-1.46) across models. Insufficient vaccine information, perceived vaccine unsafety, and distrust in the Ministry of Health were the dominant predictors. Discussion: The three models achieved comparable, clinically meaningful discrimination, and algorithmic complexity did not improve prediction over standard regression. Hesitancy was more strongly predicted by information access and institutional trust than sociodemographic disadvantage. Conclusion: These findings support trust-building engagement over broad demographic campaigns.

BackgroundSince the COVID-19 pandemic, parental delays and refusals of well-established, safe, and effective childhood vaccinations have contributed to the resurgence of infectious diseases. This raises concerns that COVID-19 vaccine hesitancy may also extend to novel vaccines for children when introduced in the future. This study examined caregivers, who included healthcare workers (HCWs), perceptions of novel vaccinations for children ages 0-17 years old and intentions to vaccinate children and adolescents ages 12-17 years against COVID-19. MethodsWe conducted a secondary data analysis of a larger cross-sectional survey administered to parents/caregivers of children ages 0-17 years in Lusaka, Zambia, between 13 November and 15 December 2023. Vaccination intention for COVID-19 was specifically focused on caregivers of adolescents ages 12-17 years, following COVID-19 vaccination guidelines during the study. Descriptive statistics were used to explore demographic characteristics, vaccination history, and caregivers COVID-19 vaccination status, along with their childrens routine childhood vaccine histories and perceptions of COVID-19 and novel vaccinations. ResultsAmong 277 caregivers (66.8% women, median age: 35 years), 93.1% reported that their child had received all recommended routine childhood vaccinations. COVID-19 vaccine uptake was higher among HCWs (68.2% with [&ge;]2 doses) than among community members (40.8%) and having [&ge;]2 doses was associated with higher COVID-19 vaccine uptake among their adolescents ages 12-17 years. 58.0% of caregivers indicated that their 12-17 years old adolescents had received at least one COVID-19 vaccine dose. Overall intention to further vaccinate children against COVID-19, especially among those already unvaccinated, remained low, with 24.7% of caregivers reporting no intent to vaccinate their children. Protection from hospitalization and death from malaria, TB, HIV, pneumonia, influenza, and diarrheal diseases were the most cited reason (79.1%) for intention to vaccinate children with novel vaccines for these diseases. The most prominent reasons for reluctance towards future vaccines were the fear of potential side effects (45.5%) and insufficient knowledge about vaccination benefits and risks (31.8%). Caregivers most trusted the Ministry of Health (86.6%) and healthcare professionals (66.8%) as sources of vaccine information. ConclusionsWhile routine childhood vaccine uptake remained high, acceptance of COVID-19 and future novel vaccines for children was lower and was influenced by caregivers own vaccination status. Targeted and transparent communication through trusted sources such as the Ministry of Health and healthcare professionals may be critical for addressing safety concerns and strengthening confidence in novel childhood vaccines.

Seeking a simple vaccine to protect against all cancer-associated human papillomaviruses (HPV), L2 residues 17-36 of both HPV16 and HPV31 displayed on the surface of an Adeno-Associated Virus-Like Particle (AAVLP-HPV) was developed. Here, a phase 1 randomized, placebo-controlled, double-blind clinical study has been conducted in 20 male and female subjects at a single dose level (20 ug) without an adjuvant. AAVLP-HPV vaccine administration was safe and well tolerated. Repeat vaccination with AAVLP-HPV elicited L2-specific neutralizing antibodies of modest titer in serum. Antibodies cross-reactive with L2 of diverse HPV types were detected, but responses were weak in most vaccinees. We conclude that while AAVLP-HPV vaccination is well tolerated, an adjuvant is likely needed to consistently elicit durable and broadly neutralizing responses.

Introduction:Although the COVID-19 pandemic clearly showed the potential consequences of a world without vaccinations, vaccine hesitancy is likely to be more pronounced in the post-COVID-19 era. The introduction of human papillomavirus (HPV) vaccines in this context is likely to raise particular concerns. In Tunisia, decision-makers have prioritized the introduction of HPV vaccine into the immunization schedule. This study assessed individual barriers and facilitators to HPV vaccine acceptability in Tunisia, with the aim of guiding an effective communication strategy for HPV vaccination campaigns in Tunisia and neighboring countries in a post-pandemic context.Methods: Using a qualitative design, we conducted 14 focus groups (FG) with healthcare professionals (HCP) (N=32) and community representatives (CR) (N=89) in five regions of the country. The discussion followed a semi-structured guide designed on the basis of vaccine hesitancy determinants matrix. Transcripts were deductively analyzed according to the 'social processes' and 'thinking and feeling' of the behavioural and social drivers (BeSD) Framework. Inductive approach was used to analyze participants suggestions for promoting HPV vaccination.Results:The FG analysis demonstrated that the historically strong trust in vaccination in Tunisia has weakened after the COVID-19 pandemic. Mistrust of health system and experts, the pandemic management and vaccine mandates measures had negative influence on the vaccine attitudes in a post pandemic Tunisian context. Persistent concerns about COVID-19 vaccines safety were frequently intertwined with widespread distrust of pharmaceutical companies and their profit motives, perceived as imposing inequitable access and lower-quality vaccines on countries in the Global South. These concerns fueled confusion about vaccines side effects. The weakening of immunity was recurring, as well as memory issues, impacts on fertility, and sudden deaths. Regarding information, our research revealed that although digital platforms were perceived as widely used, a significant part of the population interviewed considered public TV channel, as the most reliable source of health information.Conclusions: Emphasizing how the pandemic has shaped individual and collective perceptions and attitudes toward vaccination, our findings underline the importance of leveraging lessons learned from the pandemic to develop a context tailored and coherent communication strategy for successful HPV vaccine implementation.

There is currently no clinical data for the effectiveness of the only licensed Ebola virus disease vaccine (Ervebo) against Bundibugyo virus disease. A number of studies have shown immune cross-reactivity with Bundibugyo virus after Ervebo vaccination. However, antibody recognition of Bundibugyo is around 2.8-fold lower than recognition of Ebola virus. Here, we aimed to infer how a 2.8-fold drop in immune recognition may affect Ervebo protection against Bundibugyo virus disease based on analysis of data on Ervebo immunogenicity and protection from Ebola virus disease. This work has three main components. Firstly, we analysed the timing of vaccine protection in the Ervebo pivotal ring vaccination clinical trial. Secondly, we performed a systematic review and meta-analysis of antibody responses to Ebola virus after Ervebo vaccination over time. Thirdly, we combined these data with previously reported data on the cross-reactivity to Bundibugyo virus to infer protection of Ervebo against Bundibugyo virus disease. We find that the clinical trial data for Ervebo supports vaccine protection beginning earlier than 10 days after vaccination. Secondly, binding antibody levels against Ebola virus on day 28 post vaccination (peak responses) were on average 12.9-fold (95% confidence interval, CI: 6.4 - 26.0) higher than on day 7, 6.3-fold (95% CI: 3.7 -10.8) higher than on day 10, and 2.5-fold (95% CI: 1.4 - 4.4) higher than on day 14 (neutralising antibodies showed similar results). Finally, we consider the scenarios where antibody levels to Ebola virus at day 7 or 10 are putative protective thresholds against Ebola virus disease, and we assume these thresholds also apply for Bundibugyo virus disease. Then, with a 2.8-fold reduction of responses to Bundibugyo compared to Ebola virus, we predict antibody responses to Bundibugyo virus after Ervebo vaccination are likely above these putative protective thresholds.

The continued evolution of SARS-CoV-2 has led to regular updates of the COVID-19 vaccine immunogen. However, the exact benefits of these updates for vaccine effectiveness in a real world context are difficult to evaluate. We performed a comprehensive meta-analysis of booster vaccine effectiveness in studies identified through the ViewHub systematic review. We integrated evidence from 44 studies reporting on effectiveness of mRNA booster vaccines containing XBB.1.5, JN.1 and KP.2 immunogens to assess the combined impact of booster immunogen, time since vaccination and calendar time at which a study was conducted. We estimate that the relative risk of severe disease increases by 9% [95%CI 7.4-10.5] each month following booster administration, likely due to antibody waning, and by an additional 2.4% [95%CI 1.2-3.6] for each calendar month, likely due to antigenic drift. Our findings show that COVID-19 booster vaccine effectiveness declines both with time after vaccination as well as calendar time since the vaccine immunogen emerged. This reinforces the need for regularly and timely vaccine immunogen updates.

Development of an effective HCV vaccine requires the induction of both broadly neutralizing antibodies (bnAbs) and a robust cellular response. One issue that has arisen is that HCV subunit vaccines have limited immunogenicity, thus requiring multivalent formats in order to elicit a robust anti-HCV immune response. Toward that end, nanoparticle vaccines possess the ability to facilitate a controlled multivalent presentation and trafficking to lymph nodes, where they can interact with both arms of the immune system. Here, we used a soluble, secreted form of E1E2 (sE1E2) to assemble native E1E2 into a nanoparticle platform using a post-purification coupling assembly system. Nanoparticles were assembled by purifying sE1E2 containing a C-terminal SpyTag and an mi3-SpyCatcher fusion separately and covalently coupling the components via incubation. Free sE1E2-SpyTag was removed from nanoparticle preparations via gel filtration. The sE1E2-mi3 nanoparticles are fully competent to bind conformation-dependent bnAbs, indicating retention of a native assembly in the nanoparticle format. Electron microscopy analysis showed a clear incorporation of sE1E2 on the surface of the nanoparticle. Immunogenicity of sE1E2-mi3 nanoparticles was examined relative to sE1E2 alone and membrane-bound E1E2 (mbE1E2) following inoculation of groups of CD1 mice. Assessment of the immunogenicity of the sE1E2-mi3 nanoparticles showed that the nanoparticle assembly has a similar immunogenicity profile to that of mbE1E2 after only a prime and one boost, and overall superior to sE1E2. This proof-of-principle study sets the stage for further exploration of nanoparticles and other multivalent platforms for the development of E1E2-based vaccines. ImportanceHepatitis C virus infects approximately 50 million people, and at present no effective HCV vaccine exists. Due to the high sequence variability of HCV and the resulting difficulty in developing a vaccine that elicits a broadly neutralizing response, multiple efforts are underway to enhance the immunogenicity of HCV vaccine candidates. In this study, we incorporated native soluble, secreted E1E2 (sE1E2) into a 60-mer nanoparticle via the SpyTag-SpyCatcher system and covalent isopeptide bond attachment using the purified components. These nanoparticles are antigenically intact and elicit a neutralizing antibody response at an earlier time point in the immunization regimen than the corresponding subunit vaccine. These studies show that a well-characterized sE1E2 platform compatible with multiple genotypes can be coupled to nanoparticles for use as a vaccine candidate.

Monkeypox, caused by MPXV, has become a global public health concern; however, the T-cell immunity against MPXV following smallpox vaccination remains unclear. In this study, we screened the immunogenicity of 21 predicted MPXV epitopes and compared immune responses between young and elderly groups. Two immunogenic CD8 T-cell epitopes, M15 and M17, were identified, both of which effectively stimulated specific immune responses, with significantly stronger responses observed in the young group. Notably, this study provides the first evidence that smallpox vaccination induces CD8 T-cell immunity that cross-recognizes the MPXV epitopes M15 and M17 and remains detectable for more than four decades after vaccination, as demonstrated in vaccinated individuals aged 53-75. These findings provide experimental evidence for understanding the cross-protective mechanisms of the smallpox vaccine and informing monkeypox vaccine development.