Vaccines

Pneumonia remains a leading cause of global child mortality. Following the Pneumococcal Conjugate Vaccine (PCV) introduction in Yogyakarta, Indonesia, uptake for the primary series (PCV1 and PCV2) exceeded 90%. However, PCV3 coverage remained suboptimal (60% in 2023; 75% in 2024), indicating significant dropout. This study aimed to identify determinants of PCV immunization completeness and timeliness to address this gap. We conducted a cross-sectional study using cluster sampling among 405 caregivers of children aged 13-37 months in Yogyakarta City in March 2025. Data were collected via structured digital questionnaires assessing socio-demographics, perinatal conditions, knowledge, support systems, and attitudes toward multiple injections. Multivariate logistic regression was employed to determine factors associated with PCV immunization completeness and timeliness. Of 398 participants (98.3% response rate), the majority were female (95.7%) and housewives (75.1%). The prevalence of PCV completeness was 66.3%, while timeliness was only 36.4%. Multivariate analysis revealed that acceptance of multiple injections was the strongest predictor for both completeness (aOR 49.18; 95% CI: 21.30-113.50) and timeliness (aOR 22.04; 95% CI: 6.55-74.08). Additionally, home ownership (aOR 1.93; 95% CI: 1.04-3.58) was associated with completeness, whereas high knowledge (aOR 1.85; 95% CI: 1.12-3.03) improved timeliness. Conversely, preterm birth was significantly associated with lower odds of timeliness (aOR 0.29; 95% CI: 0.09-0.88). Acceptance of multiple injections emerged as the most critical modifiable factor for both outcomes. To optimize the PCV program, health authorities should prioritize counselling strategies to alleviate parental concerns regarding multiple injections. Additionally, intensified monitoring for preterm infants is crucial to mitigate immunization delays.

ObjectiveAlthough COVID-19 vaccination is important for People Living with HIV given their elevated infection and comorbidity risks, some PLHIV are hesitant to accept vaccination. Hence, we conducted a cross-sectional study in British Columbia, Canada, aimed to identify socio-economic and health-related factors predicting COVID-19 vaccine uptake and contributing to hesitancy among PLHIV. MethodsA 34-item anonymous self-administered survey was disseminated to PLHIV accessing services through HIV and AIDS-related organisations e-newsletters between November 2022 and January 2023 in British Columbia. The survey included sociodemographic information, COVID-19 factors, HIV indicators, and the Vaccine Hesitancy Scale. Descriptive and inferential statistics were conducted to detect significant associations between the sociodemographic characteristics, health-related factors and COVID-19 vaccine uptake using IBM(R) SPSS(R) 28 and significance level at p<0.05. ResultsFrom the 276 respondents (mean age 29.93{+/-}7.55), 54.7% were men, 31.6% identified as sexual minorities, and 46.7% were of indigenous origin. Approximately 40% of the respondents received at least three vaccine doses, while 82.2% received at least one dose. Vaccine hesitancy was associated with lower education, age <44, and low income. Predictors of COVID-19 vaccine uptake included age [OR=1.06, 95% CI=1.01-1.12], bachelors degree [OR=0.22, 95% CI=0.07-0.72], family/friends infected with COVID-19 [OR 3.68 95% CI=1.56 - 8.67], HIV viral load >500 copies [OR=0.20, 95% CI=0.06-0.61], belief in vaccine importance [OR= 0.51, CI=0.28-0.95], trust in Health Canadas information [OR 0.49 CI=0.29-0.83], and concerns about vaccine adverse effects [OR=0.35, CI=0.22-0.56]. Concerns about vaccine adverse effects reduced the likelihood of receiving three COVID-19 vaccine doses by 65%. ConclusionsConsiderations must be taken around specific factors that may have an impact on COVID-19 vaccination rates among PLHIV, including information about vaccine adverse effects, HIV viral load, age, and education level. This insight should guide the development of policies and interventions aimed at encouraging individuals to maintain an up-to-date vaccination status.

In October 2025, mpox virus clade I infections have been detected among men who have sex with men (MSM) in the EU/EEA, suggesting local transmission in MSM sexual networks. Given the large outbreak of mpox among MSM in 2022 and the uncertain transmission parameters of clade I in the European context, clade I poses a public health concern to the EU/EEA. This work assesses the potential effect of increasing the mpox vaccine uptake among MSM via two contributions. First, building on the European MSM and Trans Persons Internet Survey 2024, we estimate the mpox vaccine uptake among MSM as well as the proportion who are unvaccinated but willing to get vaccinated for 28 countries in the EU/EEA. Specifically, we fit Bayesian mixed-effects models for the vaccine and recovery status of an individual depending on their number of sexual partners and country. Second, we develop a susceptible-infectious-recovered model on a sexual contact network to estimate the reduction of the reproduction number if vaccines are provided to MSM who are willing to get vaccinated. Our results suggest a substantial willingness for mpox vaccination among MSM if mpox cases increase and a large reduction of the effective reproduction number if this willingness is met. These findings highlight a large potential of increasing mpox vaccine uptake among MSM and preventing future mpox outbreaks in the EU/EEA.

While vaccination conflicts have become apparent, physicians' attitudes toward those with differing views remain unclear. Through an online survey of 492 physicians and 5,252 members of the general public in Japan in February 2026, we investigated attitudes toward four vaccines (influenza, measles, HPV, and COVID-19). Intergroup bias was assessed as ingroup minus outgroup attitudes using a feeling thermometer. Multilevel regression examined associations with agreement group and physician status. Intergroup bias was significantly positive in both agreement and disagreement groups across all vaccine types, and was higher in the agreement group. Physicians exhibited higher intergroup bias than the general public. These findings indicate that vaccination conflict is bidirectional: physicians, often viewed as targets of hostility from vaccine-hesitant individuals, themselves exhibit greater intergroup bias toward those with opposing views. Interventions to raise physicians' awareness of their own bias, alongside communication strategies for vaccine-hesitant individuals, are needed.

BackgroundNeisseria gonorrhoeae poses significant public health challenges due to multidrug-resistant gonorrhoeic and severe reproductive health complications of untreated infection. No vaccine is licensed to prevent gonorrhea. However, the meningococcal outer membrane vesicle (OMV)-containing vaccine, 4CMenB, provides moderate cross-protection against gonorrhea. We have recently demonstrated that immunization with gonococcal OMV accelerates clearance of gonococcal infection in mice compared with 4CMenB. MethodsTo gain insight into possible mechanisms of protection of gonococcal OMV, we evaluated the immunogenicity of GonoVac, a candidate native OMV (nOMV) vaccine against gonorrhea, in mice and rabbits. Three doses of GonoVac were administered intramuscularly from 0.15 to 5 {micro}g in mice, and four doses were used to immunize rabbits at 50 {micro}g per dose, formulated with or without aluminum hydroxide (Al(OH)3). Systemic and mucosal antibody responses were evaluated by enzyme-linked immunosorbent assay (ELISA) and serum bactericidal assay (SBA). Cellular responses were assessed by enzyme-linked immunosorbent spot (ELISpot). ResultsImmunization with GonoVac formulated with and without Al(OH)3 induced significantly higher levels of gonococcal serum and vaginal IgG, and serum bactericidal antibodies, compared with 4CMenB, which induced no serum killing activity. Serum bactericidal activity of GonoVac correlated with anti-gonococcal IgG and IgG2a levels. Serum IgA levels were minimal. Cellular immune responses were higher in mice receiving GonoVac/Al(OH)3 compared with GonoVac alone. Immunogenicity was similar for GonoVac produced in a bioreactor and shake flasks. ConclusionGonoVac elicits robust and functional immune responses in mice and rabbits compared with 4CMenB, supporting its further development as a promising candidate vaccine against gonorrhea. ImportanceGonorrhea, caused by Neisseria gonorrhoeae, remains a significant global health concern, disproportionately affecting populations in low- and middle-income countries (LMICs), particularly women. The emergence of multidrug-resistant strains of N. gonorrhoeae has raised the concern of untreatable gonorrhea, underscoring the urgent need for effective preventive measures. Although there is no licensed vaccine against gonorrhea, the meningococcal OMV-based vaccine, 4CMenB, is partially effective against the disease and has been recommended for use in high-risk groups. In this article, we build on previous findings of enhanced efficacy of gonococcal OMV vaccine candidates compared with 4CMenB in the mouse gonococcal infection model to demonstrate the superior anti-gonococcal immunogenicity of a gonococcal OMV-based candidate vaccine (GonoVac) compared with 4CMenB. GonoVac elicits robust immunity in mice, inducing antibodies that are able to kill gonococci, whereas 4CMenB does not. The findings highlight the potential of GonoVac as a promising vaccine candidate for the prevention of gonorrhea worldwide.

Background Ever since the COVID-19 vaccine became available, vaccinations in adolescents lagged behind adults. Whether adolescent vaccination rates were higher in states with "Minor Consent" policies remains unknown. Methods We accessed adolescent (aged 12-17) county-level vaccine administration data from the CDC (12/2020-05/2023). Our outcomes were COVID-19 vaccination counts for: 1) initial dose, 2) completed series doses, and 3) booster doses. Panel Poisson regression models with state and time random effects, seasonal fixed effects, log-population offsets, and adult vaccination rates were estimated to calculate incidence rate ratios (IRR), testing the association between residing in a state with a Minor Consent policy and COVID-19 vaccine uptake. Results Overall, for the initial dose and complete series, there was no difference in adolescent COVID-19 vaccination between states with or without Minor Consent policies. However, we found that Minor Consent policies were associated with lower COVID-19 booster doses (IRR = 0.582; 95% CI: 0.409, 0.828; p = 0.0026). This association was not found in urban counties (IRR = 0.867; CI = 0.722, 1.043; p = 0.1295), but only in rural counties (IRR = 0.541; CI = 0.401, 0.730; p < 0.0001). Conclusions Minor Consent policies were not associated with higher adolescent COVID-19 vaccination. Rather, we found that Minor Consent policies were associated with lower adolescent vaccination for booster doses in rural counties. Despite minimal evidence of impact, states continue to implement Minor Consent vaccination policies. Future research should investigate not just other vaccines, but also how Minor Consent policies impact parental trust in public health more broadly.

The assessment of pneumococcal vaccine response currently relies on a single IgG concentration threshold, identical for all serotypes, as recommended by the WHO and AAAAI. However, the recommended thresholds do not take the wide inter-serotype variability into account. The purpose of this study was to determine if the antibody threshold linked to a functional immune response varies according to serotype. We performed a retrospective analysis on 729 samples from adults at risk of invasive pneumococcal disease (IPD), sent between 2018 and 2024 to assess vaccine response. Specific IgG concentrations for seven vaccine serotypes were measured by ELISA and compared to opsonophagocytic assay (OPA) results, a functional test considered as the gold standard. For each serotype, we determined the most predictive IgG concentration (PIC) for a positive OPA result using ROC curves, Youdens index, and bootstrap analysis with 1,000 resamples. The resulting PIC were then compared using non-parametric tests (Kruskal-Wallis test followed by Dunns post-hoc test with Holms correction). The PIC varied considerably among serotypes, ranging from 0.84 to 4.74 {micro}g/mL. This variability was found to be statistically significant (p<0.0001). Areas Under the Curve (AUC), ranging from 0.73 to 0.87, demonstrate good diagnostic performance. Overall, the application of serotype-specific thresholds in patients significantly change the classification of vaccination status compared to a single threshold (Cochran, McNemar). These results indicate that the protective antibody threshold is not universal. A serotype-specific approach would allow a more precise and relevant assessment of the pneumococcal vaccine response. Author summaryThe introduction of the 7-valent pneumococcal conjugate vaccine (PCV-7) in the early 2000s significantly changed the epidemiology of invasive pneumococcal disease by modifying serotype distribution. However, vaccine-induced immunity varies across serotypes, and this heterogeneity remains incompletely understood. In this study, we first assessed differences in vaccine responses according to serotype. We then determined predictive serotype-specific immunoglobulin concentration for the seven routinely serotypes tested in our laboratory, defined as the minimal levels required to induce a positive opsonophagocytic activity (OPA) response. The results enable a more accurate assessment of serotype-specific vaccine immunity, supporting improved patient stratification and guiding booster vaccination in individuals with insufficient responses.

COVID-19 remains a substantial public health challenge in the Netherlands. Next-generation COVID-19 vaccine, mRNA-1283, is approved in the European Union, with potential for higher relative vaccine efficacy compared with originally-licensed COVID-19 vaccines. Its potential public health and economic impact, in adults [&ge;]60 years and high-risk 18-59 years, was modelled versus no vaccination and originally-licensed mRNA-1273 and BNT162b2, adapting a published static Markov model with 1-year time horizon. COVID-19 burden reflected two full post-pandemic seasons. Vaccine efficacy versus mRNA-1273 was based on pivotal phase 3 NextCOVE trial data; efficacy versus BNT162b2 was derived from an indirect treatment comparison. The economically justifiable price (EJP) of mRNA-1283 versus no vaccination, and price premiums over existing vaccines, were determined at a willingness-to-pay threshold of {euro}50,000/quality-adjusted life-year (QALY) gained. Without COVID-19 vaccination, an estimated 460,000 infections, 23,800 hospitalizations and 5,300 deaths would occur. With current coverage, mRNA-1283 was estimated to prevent 68,000 infections, 5,400 hospitalizations, and 1,200 deaths, saving 9,667 QALYs and over {euro}66.5 million in treatment costs. The EJP was {euro}238 versus no vaccination. Compared with mRNA-1273 and BNT162b2, mRNA-1283 was estimated to prevent additional burden (e.g., 1,309 and 1,679 hospitalizations, respectively), and was cost-effective at an incremental EJP of {euro}62 versus mRNA-1273, and {euro}80 versus BNT162b2. The results support continued COVID-19 vaccination to mitigate the ongoing health and societal burden of SARS-CoV-2 in the Netherlands. The comparative analyses indicate that mRNA-1283 may be associated with substantial health benefits over originally-licensed mRNA vaccines; consequently, its use may further improve health outcomes and economic efficiency within COVID-19 vaccination programs.

Background: Understanding the underlying mechanisms for differences in vaccine uptake between migrants and non-migrants is crucial in order to design targeted interventions encouraging vaccination and to ensure vaccine-related equity. Therefore, this study examined to what extent migration-related disparities in COVID-19 vaccination were associated with psychological factors, based on the established 5C model of vaccine behaviour (Confidence, Complacency, Constraints, Calculation, Collective Responsibility). Methods: Data were obtained from the German study "Corona Monitoring Nationwide - Wave 2" (RKI-SOEP-2 study), which was carried out between November 2021 and March 2022. The association between COVID-19 vaccination and migration status, while considering the psychological factors, was investigated using multivariable binary logistic regressions. A decomposition analysis (Karlson-Holm-Breen method) was conducted to examine the extent to which migration-related disparities in vaccine uptake were associated with the psychological factors of the 5C framework. Results: Migrants were less likely to be vaccinated against COVID-19 compared to non-migrants, especially participants from the Middle East and North Africa (MENA) region. Our decomposition showed that almost two-thirds of the disparities in COVID-19 vaccine uptake between migrants and non-migrants were associated with the psychological factors (first-generation: 61.2%, second-generation: 64.2%). Confidence in safety of the vaccine was the most relevant factor in the 5C framework. Furthermore, the results highlighted the importance of a differentiated analysis regarding country of origin: While the 5C model accounted for only 19.4% of the difference between participants from the MENA region and non-migrants, the proportion for participants from Eastern Europe was 73.5%, suggesting that the underlying mechanisms for the lower uptake in the MENA group need further investigation. Conclusions: Overall, migration-related disparities in COVID-19 vaccination were significantly associated with differences in psychological factors of vaccine behaviour. To increase vaccine acceptance within the heterogeneous group of migrants in general, tailored and proactive health communication interventions are needed.

Objectives: Influenza is a widespread acute respiratory illness posing a major public health challenge for both the National Health Service (NHS) and society, particularly among older adults. This study aimed to assess the cost-effectiveness of high-dose quadrivalent vaccine (HD-QIV) versus adjuvanted quadrivalent vaccine (aQIV) in older adults in Spain. Methods: Public health and economic benefits were evaluated using a decision-tree model considering influenza cases, GP and ED visits, hospitalizations, and influenza-related mortality. Deterministic and probabilistic sensitivity analyses addressed epidemiological and economic uncertainties. Results: From a societal perspective, HD-QIV prevented 54,039 influenza cases, 7,733 GP consultations, 1,585 ED visits, 27,398 episodes of hospitalization due to cardiorespiratory events over a single influenza season and 1,203 deaths compared to aQIV when vaccinating adults [&ge;]65 years old in Spain, resulting in 14,316 LYs and 12,440 QALYs gained over a lifetime horizon. The reduction in health outcomes outweighed the increase in vaccination costs, translating to a reduction in total costs with HD-QIV compared to aQIV. Therefore, vaccinating older adults in Spain with HD-QIV instead of aQIV was a dominant strategy when evaluating hospitalizations due to respiratory and cardiovascular events. HD-QIV remained dominant from a NHS perspective. Sensitivity analyses confirmed the robustness of the model. Conclusions: This analysis showed that vaccinating older adults in Spain with HD-QIV instead of aQIV would reduce influenza cases, GP and ED visits, hospitalizations, deaths, and associated costs, and thus it should be the strategy of choice in a situation of budgetary constraints from either a societal or an NHS perspective.

Background Vaccine-preventable diseases (VPDs) continue to impose a significant health and economic burden globally, despite advances in immunization programs. Narrower to the context of Saudi Arabia, the current literature consistently shows that the high vaccination coverage has had the primary impact of reducing disease incidence. Regardless, the broader economic impact of VPDs and the financial benefits of immunization remain important for policy evaluation within Saudi Arabia. Methods This study employed a model-based economic evaluation using a societal perspective in order to carry out an estimation of the economic burden of measles, influenza, and pneumococcal diseases. We utilized the Cost of Illness (COI) approach for the purpose of quantifying direct medical costs and indirect productivity losses. On the other hand, the Value of Statistical Life (VSL) approach helped in the estimation of the monetary value of mortality reduction. A comparative framework analyzed current vaccination coverage against a counterfactual no-vaccination scenario for the calculation of the return on investment (ROI). Results The estimated annual economic burden of the three selected VPDs in the absence of vaccination was USD 385 (95% CI: 315-460) million. Immunization programs generated substantial economic benefits, with total benefits estimated at USD 1085 (95% CI: 815-1360) million annually. The calculated ROI was 9.0 (95% CI: 6.8-11.3), essentially an indication that for each dollar invested in vaccination, there was multiple economic returns yielded. Sensitivity analyses confirmed the robustness of these findings. Conclusion Immunization programs in Saudi Arabia provide significant economic and public health benefits and for this reason, sustained investment in vaccination is fundamentally essential towards the reduction of disease burden, improve population health, and ultimately support long-term economic productivity.

Dengue disease remains a significant global health threat, with current vaccines exhibiting variable efficacy and safety concerns. Virus-like particles (VLPs) offer a promising alternative by mimicking native virus structures without infectious genomes. We engineered a mammalian expression plasmid encoding Dengue-1 prM and E proteins, optimized for secretion using Japanese Encephalitis virus signal sequences, and transiently expressed it in HeLa cells. Purified VLPs exhibited spherical morphology ([~]39 nm diameter) consistent with native virions, as confirmed by transmission electron microscopy. Immunization of mice with these VLPs elicited robust Dengue-1 specific IgG antibody responses. Our study demonstrates production of immunogenic Dengue-1 VLPs in HeLa cells, highlighting their potential as a vaccine candidate and a tool for serodiagnosis. Further characterization of VLP epitopes and protective efficacy is warranted to advance vaccine development. ImportanceDengue remains a significant global health challenge, with serotype 1 being one of the dominant strains causing recurrent outbreaks in Nepal. Existing vaccines demonstrate limited efficacy and pose significant safety concerns, particularly in seronegative populations. To address these limitations, this study explores virus-like particles (VLPs) as a safer alternative vaccine platform. VLPs elicit robust immunogenicity by mimicking the structure of native virus while completely lacking genetic components. This study combines DENV1 structural proteins with optimized expression systems to enhance immunogenicity. This work is particularly significant as the first dengue vaccine research conducted in Nepal, directly addressing antigenic mismatches between existing commercial vaccines and locally circulating viral strains. Furthermore, the study provides scalable platform for developing region-specific dengue vaccines for other serotypes and flaviviruses.

Introduction The link between Human Papillomavirus (HPV) and cancer is well-established. In Singapore, bivalent HPV vaccines are subsidised for females, but not males. Economic analysis of HPV vaccination has generally assessed the costs to the health system, but this may not be as relevant to individual decision-making as potential lost income. We estimated the impact of bivalent HPV 16/18 vaccination on sick leave, unemployment, and premature mortality as a function of age and sex to understand the broader impact of HPV-related cancers. Methods We developed a population-level economic model to estimate lifetime income losses by diagnosis age, sex and cancer type. We applied sex- and cancer-specific Cox regressions to the Singapore Cancer Registry for annual predicted survival from 1992 to 2022. These were combined with census and employment data to estimate HPV-associated income losses in Singapore. Attributable fractions and vaccine effectiveness data for HPV 16/18 from the literature were used to estimate the effectiveness of bivalent HPV vaccination. Structural sensitivity analysis examined the role of 80% population coverage conferring herd immunity. Results The registry contained 17,294 individuals with an HPV-associated cancer diagnosis. Lost income was greatest for cervical cancer due to its high prevalence, however the losses per diagnosis were highest for oropharyngeal cancer. Bivalent HPV vaccination led to income benefits of $SGD1,397 [$895 to $1,838] in girls and -$62 [-$76 to -$48] in boys. A gender-neutral HPV vaccination of 80% of 15-year-old Singaporeans, conferring herd immunity, would have lifetime income protective benefits of $24.4m [$14.2m, $33.7m] per cohort, a five-fold return on investment. Conclusions In addition to avoiding healthcare costs and lost quality of life, parents should consider vaccination as a means of avoiding potential income losses. A national policy of gender-neutral HPV vaccination could deliver substantial income protection due to both individual vaccine protection and herd immunity.

Background To anticipate the impact of new pneumococcal vaccines and guide future updates, accurate forecasts of changes in non-vaccine serotypes (NVTs) are needed. We developed and evaluated three models that incorporated different assumptions about the way in which NVTs will increase and generated ensemble predictions for the frequency of NVTs in different post- pneumococcal conjugate vaccines (PCV) periods. Methods We analyzed age- and serotype-specific invasive pneumococcal disease (IPD) cases from the United States CDCs Active Bacterial Core surveillance during the pre-PCV (1998-1999), early post-PCV7 (2000-2004), late post-PCV7/pre-PCV13 (2005-2009), early post-PCV13 (2010-2014), and late post-PCV13 (2015-2019) periods. These data were augmented with IPD cases from several countries and combined with serotype-specific invasiveness to infer serotype-specific carriage prevalence. Three models (Ranking, Proportionate, NFDS-lite) generated independent predictions of post-PCV IPD frequencies, which were integrated using an accuracy-weighted ensemble. Model performance was evaluated using the normalized root mean square error (NRMSE). Results A total of 23,959 non-PCV7 and 15,580 non-PCV13 cases were analyzed. NVT cases increased from the pre-PCV7 to the late post-PCV7 and post-PCV13 periods. The accuracy of predictions across age groups and models was consistent and high during the post-PCV13 periods but varied during the post-PCV7 periods. The Proportionate model (NRMSE=0.70-3.95) outperformed the NFDS-lite (NRMSE=0.93-8.91) and Ranking (NRMSE=1.51-5.37) models during the early-post-PCV7 period, whereas the NFDS-lite model (NRMSE=1.55-9.82) was superior to the Proportionate (NRMSE=1.45-10.22) and Ranking (NRMSE=1.86-11.35) models during the late post-PCV7 period. The Ensemble model improved on these individual models. Conclusions The Ensemble model offers a tool for forecasting serotype patterns to inform pneumococcal vaccines impact and future pneumococcal vaccine formulation.

Human Cytomegalovirus (HCMV) is an omnipresent pathogen that is associated with increased morbidity and mortality of immunocompromised individuals. Studies of T-cell immunity to HCMV primarily reflect anti-CMV pp65 or immediate early antigen 1 (IE-1) activity. Recent evidence highlights the importance of the major immediate-early 2 (IE2) protein, which is expressed early after HCMV infection and reactivation, for regulating the lytic HCMV replication cycle. In this study, we designed a comprehensive screening approach to assess T cell responses against the IE2 HCMV protein in the peripheral blood of 15 HCMV-seropositive and 6 HCMV-seronegative healthy adults using IE2 synthetic long peptide (SLP) pools and cytokine flow cytometry. The T cell response against the IE2 protein was dominated by CD4+ T cells whereas IE2-specific CD8+ T-cell reactivity was measured in only 3 donors. Most of the donors recognized chiefly the IE2351-434 residues, revealing a remarkably immunogenic area of the protein. Numerous novel HLA class I- and II-restricted IE2 T-cell epitopes were identified. Functional characterization of the IE2 CD4+ and CD8+ T cell responses uncovered 5 highly antigenic SLPs, which induced polyfunctional Th1 cytokine (IFN-{gamma}+/ TNF+/ IL-2+) response and could serve as candidate vaccine antigens. Evaluation of these 5 highly antigenic IE2 SLPs in T cell-inducing vaccines aiming to inhibit HCMV infection by targeting the expression of immediate-early genes is warranted.

BackgroundThe LP.8.1-containing COVID-19 mRNA vaccines were recommended for the 2025 seasonal vaccination campaigns in Europe and the United States. Safety data on these vaccines are limited. MethodsWe conducted a nationwide register-based cohort study in Denmark including all adults aged 65 years and older or at high risk of severe COVID-19 who had received previous COVID-19 vaccine doses. The study period was July 1, 2025, to December 3, 2025. We estimated incidence rate ratios using Poisson regression comparing rates of 30 adverse events within 28 days following LP.8.1-containing vaccination with reference period rates, adjusted for age, sex, region of residence, high risk of severe COVID-19, calendar time, and comorbidities. Self-controlled case series analysis was conducted as a complementary approach. ResultsAmong 1,565,697 individuals (mean age 69.5 years; 53.8% female), 958,633 received an LP.8.1-containing vaccine. Receipt of an LP.8.1-containing vaccine was not associated with a statistically significant increased rate of any of the 30 adverse events within 28 days after vaccination. The incidence rate ratio was 0.95 (95% CI, 0.86-1.06) for ischemic cardiac event, 0.83 (95% CI, 0.76-0.92) for cerebrovascular event, and 0.32 (95% CI, 0.04-2.50) for myocarditis. Results from the self-controlled case series analysis were similar. ConclusionsIn a nationwide cohort of more than 1.5 million adults, no increased risk of 30 adverse events was observed following vaccination with LP.8.1-containing COVID-19 mRNA vaccines.

The emergence of vaccine covered serotypes causing invasive pneumococcal disease (IPD) is a serious concern worldwide. We investigated the unexpected rise of serotype 4 causing IPD primarily in non-vaccinated young adults after the COVID-19 pandemic that further spread to adults [&ge;] 65 years in recent years. For this purpose, we conducted a retrospective study of serotype 4 IPD cases (n=827) reported in Spain between 2009 and 2024. Whole-genome sequencing was performed to assess clonal lineages and phylogenetic relationships. Clinical and epidemiological data were compared between serotype 4 and all other serotypes causing IPD. Epidemiological and genomic analysis confirmed that the rise started as an abrupt cluster of IPD cases in Seville (Andalusia) in the year 2022 due to the ST15063 within GPSC12 lineage. This outbreak initially caused pneumonia episodes that required hospitalization in young individuals associated with high rates of tobacco smoking, alcohol, and inhaled drugs such as cannabis and cocaine, followed by a general distribution pattern throughout the country in the following years, affecting the elderly population. Experimental studies to evaluate potential underlying mechanisms confirmed that ST15063 serotype 4 strains displayed enhanced infection rates of human lung cells that significantly increased in the presence of cigarette smoke exposure and by influenza H3N2 virus coinfection, but not with H1N1. These findings highlight the need for targeted vaccination strategies not only against pneumococcus but also against respiratory viruses such as influenza, RSV and COVID-19 and demonstrate the importance of molecular surveillance to establish effective interventions in high-risk populations.

Cameroon introduced Human papilloma virus vaccine (HPVV) into the routine immunization schedule in October 2020. By the end of 2022, coverage remained low. To increase coverage, Cameroon switched to a country-wide, gender-neutral vaccination (GNV) approach in 2023, coupled with a revamped delivery strategy consisting of Community Dialogues (CDs) and Periodic Intensification of Routine Immunization (PIRIs) activities in selected health districts (HDs). We assessed the impact of these programmatic changes, notably the GNV approach, on HPVV coverage. This retrospective, cross-sectional study measured the effect of GNV and CDs + PIRIs on HPVV coverage among 9-year-old girls in Cameroon (2022-2023). Data on HPVV coverage from all 203 HDs were extracted from DHIS2, and coverage was calculated at the HD level, based on the estimated population eligible of 9-year-old girls. Descriptive statistics and multiple regression models were employed to assess the impact of GNV on vaccination coverage while adjusting for CDs + PIRIs and urban/rural status. In 2023, of the 203 HDs, 115 (56.7%) conducted GNV only, 74 (36.5%) implemented GNV & CDs + PIRIs, and 75.9% (154) were classified as rural. Among age-eligible girls, there was an overall increase in HPV vaccination coverage, with coverage rising 39.2 percentage points from 2022 to 2023. Following multiple linear regression, there was a significant increase in HPVV coverage in HDs with GNV & CDs + PIRIs compared to those with no GNV and no CDs + PIRIs ({beta}:55.5%, 95%CI: 38.7, 72.3, p=0.000). Furthermore, there was a significant increase in HPVV coverage in HDs with GNV only compared to those with no GNV or no CDs + PIRIs ({beta}:28.7%, 95%CI: 12.5, 45.0 p=0.001). Overall, the GNV approach increased HPVV coverage for girls significantly, particularly when implemented alongside CDs + PIRIs.

ObjectiveHealthcare workers (HCWs) are at increased risk of COVID-19 infection and play a critical role in influencing public vaccine acceptance. This study aimed to assess vaccination coverage and identify the determinants of vaccine uptake among healthcare workers in Cameroon, in order to inform targeted strategies to strengthen immunization programs and improve epidemic preparedness. ResultsAmong 406 participants (75.6% female, 65.5% aged 30-44 years, 61.3% nurses), 42.4% were fully vaccinated against COVID-19, while only 4.7% had completed the cholera vaccine series. Coverage varied across districts, with Biyem-Assi (53.0%) and Odza (46.0%) recording the highest COVID-19 uptake, and Nkolndongo (11.5%) leading for cholera vaccination. Independent predictors of COVID-19 uptake included being a nurse (aOR = 3.96; 95% CI: 2.07-7.81; p = 0.001) and laboratory technician professions (aOR = 8.00; 95% CI: 1.38-69.8; p =0.032). For cholera vaccination, working in internal medicine wards (aOR=11.2; 95% CI: 1.04-120; p = 0.046) and being a nurse (aOR = 1.54; p = 0.001) emerged as significant predictors. Although 62.8% of HCWs perceived their work environment as high-risk, knowledge of recommended vaccines was limited, with only 18.7% aware of cholera vaccination recommendations. Strengthening vaccine education, improving accessibility, and reducing financial barriers could enhance vaccine acceptance among HCWs. These findings provide important insights for designing targeted immunization strategies in Cameroon and similar contexts.

BackgroundPatients with chronic immune-mediated disorders (IMIDs), including inflammatory bowel disease (IBD), are at increased risk of cardiovascular disease. While advanced therapies show cardioprotective effects in other IMIDs, their impact on major adverse cardiovascular events (MACE) in IBD remains unclear. We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating MACE risk with advanced therapies in IBD. MethodsSystematic search of PubMed, Embase and Cochrane Central identified 43 high-quality studies (36 RCTs,7 observational studies) published between 2002 and 2024. Primary analyses estimated odds ratios (OR) for MACE comparing advanced therapy to placebo, with secondary analyses stratified studies by drug class and length of follow-up. ResultsPlacebo-controlled RCTs showed a nonsignificant trend toward reduced MACE risk (OR: 0.60; 95% CI: 0.24-1.51), with similar findings after continuity correction for zero-event studies (OR: 0.87; 95% CI: 0.45-1.68). Class-specific trends suggested lower MACE risk with IL-12/IL-23 inhibitors (OR: 0.35; 95% CI: 0.05-2.21), JAK inhibitors (OR: 0.57; 95% CI: 0.16-2.06), and a potential increase with anti-TNF agents (OR: 3.04; 95% CI: 0.31-29.47), though none reached statistical significance. Long-term follow-up studies showed consistent findings. Observational studies suggested lower MACE risk for anti-TNF therapies (OR: 0.29; 95% CI: 0.21-0.40), but not for IL-12/IL-23 (OR: 4.41; 95% CI: 0.49-39.28) or JAK inhibitors (OR: 1.57; 95% CI: 0.86-2.84). ConclusionAdvanced therapies did not demonstrate a clear increase or decrease in cardiovascular risk in IBD. The discrepancies between RCTs and observational studies underscore the urgent need for rigorous-designed observational research with long-term follow-up to evaluate the real-world impact of advanced therapies on MACE risk. SummaryThis study evaluated cardiovascular safety of advanced therapies in inflammatory bowel disease. Findings showed no clear signal of decreased major cardiovascular risk compared with conventional treatment, highlighting the need for continued monitoring through long-term and real-world evidence. Key MessagesO_LIWhat is already known? Patients with IBD are at increased risk of cardiovascular events, and the impact of advanced therapies on this risk remains uncertain. C_LIO_LIWhat is new here? This meta-analysis integrates data from randomized and observational studies and found no significant association between advanced therapies and MACE. C_LIO_LIHow can this study help patient care? Findings show no clear signal of decreased cardiovascular risk with advanced IBD therapies, though continued evaluation is warranted. C_LI