ABSTRACT Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants, young children, and the elderly. Current licensed prefusogenic F-based RSV vaccines induce systemic immune responses through intramuscular injection. However, mucosal immunization will be required to elicit local sterilizing immunity to prevent virus replication in the nasopharynx and the lungs as well as virus shedding and transmission. Adenovirus vectors are a promising platform to develop RSV vaccines, but further evaluation of mucosal adenovirus-based prefusion F (preF) vaccines is still needed. In this study, we constructed a recombinant chimpanzee adenovirus serotype 68 vector expressing a second-generation disulfide-stabilized (DS2)trimeric preF protein (ChAd68-PreF). In mice, intranasal immunization with ChAd68-PreF induced dose-dependent increase in RSV-specific secretory IgA (sIgA) in the lower respiratory tract, demonstrating its capacity to elict mucosal immunity. Subsequently, in cotton rats, intratracheal instillation of ChAd68-PreF induced high cross-neutralizing antibody titers against RSV A and RSV B. After RSV A2 challenge, ChAd68-PreF vaccinated animals showed no detectable viral replication in the nose nor in the lungs. Moreover, ChAd68-PreF vaccination did not lead to enhanced respiratory disease (ERD) in cotton rats. These results demonstrate that mucosal delivery of ChAd68-PreF confers potent protective immunity against RSV with good safety profile, warranting further clinical development as a mucosa-targeting RSV vaccine for vulnerable populations.

ABSTRACT Vaccine confidence plays a critical role in public health. Understanding demographic differences in trust and sources of vaccine information is essential for designing equitable communication strategies. We analyzed nationally representative summary data from Cycle 2 of the Canadian COVID-19 Vaccine Coverage Survey (CVCS), collected April–May2021 during the initial phase of the national vaccine rollout. The survey included adults aged 18 and older (n = 10,678). This study examines trust in vaccine safety, efficacy, and information sources across demographic factors such as age, gender, and visible minority status. Trust in vaccine safety and effectiveness was high overall (95% and 97%, respectively), peaking among older adults (96% and 98%) and lower among younger males (as low as 85% for perceived COVID-19 vaccine protection). In general, public health agencies were the most trusted sources of information (84%), followed by physicians and health scientists (70%); trust in vaccine manufacturers remained low (31%). Visible minority respondents were more likely to trust public health regulations (87% vs 83%) but also more likely to prefer natural immunity (20% vs. 14%) than non-visible minorities population. These findings provide a unique population-level snapshot of vaccine trust during the critical early phase of Canada’s COVID-19 vaccine rollout. By identifying demographic differences in vaccine perceptions and information sources, our study offers an essential benchmark to inform future public health communication strategies and preparedness efforts.

ABSTRACT Although the global burden of pertussis has declined steadily over recent decades, the COVID-19 pandemic coincided with a marked disruption of its established epidemic trajectory. We assessed pandemic-associated changes using spatiotemporal trend analysis, health inequality assessment, multivariable regression, and Mendelian randomization. Globally, the age-standardized disability-adjusted life years (DALYs) rate decreased from 378.01 per 100,000 in 1990 to 70.92 in 2021, accelerating steeply after 2019. Despite reductions, burden remained concentrated in low-sociodemographic index (SDI) countries, with widening relative inequalities. Macro-scale multivariable regression stratified by SDI revealed no robust independent association between COVID-19 and pertussis incidence after adjusting for population density. Consistently, Mendelian randomization analyses found no evidence of a causal effect of genetic liability to COVID-19 on pertussis risk. These findings suggest the pandemic-era decline is driven by disruptions to transmission and health services rather than biological cross-protection. We interpret this transient suppression as contributing to an emerging immunity gap – an accumulation of susceptible individuals following reduced natural exposure and interruptions to routine immunization. As social contact patterns normalize, this immunity gap increases the risk of rebound transmission. Strengthening life-course vaccination, including catch-up programmes and prioritization of low-SDI settings, is essential to mitigate post-pandemic resurgence.

ABSTRACT This study examined whether COVID-19 Vaccine Hesitancy (VH) and COVID-19-related factors interact to influence COVID-19 booster doses uptake among university students in Canada, from a syndemic perspective. A cross-sectional survey was conducted among 4453 students at the University of Waterloo in 2024. VH was measured toward both COVID-19 primary and booster doses. Change in VH scores were computed to capture shifts in hesitancy over time. Logistic regression models assessed the main effects of VH and COVID-19-related factors on booster uptake. Interactions were tested using additive and multiplicative scales. Increased VH was associated with a 23% decrease in booster uptake. Younger ages, not being hospitalized due to COVID-19, not receiving the influenza vaccine, noncompliance with COVID-19 guidelines, and belief in conspiracy theories predicted lower booster uptake. Significant interactions were found between change in VH scores and COVID-19 diagnosis and hospitalization history, guideline adherence, and conspiracy beliefs. For students who did not receive booster doses, the change in VH was greater among those who reported following public health guidance than those who did not. Similarly, for students who did not receive booster doses, the change in VH was greater among those who reported not believing in conspiracy theories compared to those who did. The findings support a syndemic model, indicating that VH and COVID-19-related experiences jointly influence booster uptake. Targeted interventions such as rebuilding trust, addressing misinformation, and reducing stigma may improve booster uptake even if not all barriers are addressed. Further research is needed to examine these interactions.

ABSTRACT The clinical manifestation of anogenital warts (AGW) resulting from Human Papillomavirus (HPV) infection is influenced by host immune responses. Interferon (IFN)-α contributes to antiviral activity, while Interleukin (IL)-2 plays an important role in cellular immunity. Tuberculin purified protein derivative (TPPD) has been investigated as an immunotherapeutic agent. This exploratory quasi-experimental study analyzed 12 AGW patients treated with intralesional TPPD (5 tuberculin units weekly for six injections). Tissue samples were collected at baseline and week 2, and serum samples at baseline and week 6. IFN-α and IL-2 expression in tissue was assessed using immunohistochemistry (IHC), and serum levels were measured using ELISA. TPPD therapy was associated with increased IFN-α and IL-2 expression in tissue (p = .047 and p = .019) and higher serum IL-2 levels (p = .030), while serum IFN-α did not change significantly. Clinically, 4 of 12 patients achieved complete response, whereas others showed partial, minimal, or no improvement, and 6 patients required subsequent destructive treatment. Local and systemic cytokine changes did not correlate with lesion regression. These findings suggest that cytokine upregulation reflects immune activation rather than determining lesion clearance, and between-group comparisons should be interpreted cautiously due to baseline.

ABSTRACT Parental vaccine hesitancy (VH) remains a significant public health challenge in France, despite mandatory childhood vaccination policies. Motivational interviewing (MI) has shown promise in reducing VH and increasing vaccination intentions. This study aimed to evaluate the sustained impact of an MI-based intervention on VH and vaccination intentions among postpartum mothers in Southeastern France. We conducted a randomized controlled trial (RCT) in two maternity wards in Southeastern France between November 2021 and April 2022. A total of 733 mothers were randomly assigned to receive either a MI session delivered by trained midwives or an educational leaflet. We used the Parent Attitudes about Childhood Vaccines questionnaire to assess VH (0–100 score) and a single question to measure vaccination intentions (1–10 score). Data on VH and vaccination intentions were collected pre-intervention (T0), immediately post-intervention (T1), and seven months later on average (T2). Linear regression models adjusted on potential confounders and Heckman’s two-step selection method were used to analyze the data. Seven months post-intervention, we observed a reduction in VH scores (10.1/100 points, p < .0001) and an increase in vaccination intention scores (0.8/10 points, p = .01) compared to the control group. The impact of MI was consistent across different perceived financial situations. Our findings demonstrate that MI has a sustained effect in reducing VH and increasing vaccination intentions among postpartum mothers. MI should be considered as a key strategy to strengthen and sustain vaccine confidence. Further research is needed to test the impact of MI interventions among other under-vaccinated populations, such as pregnant women.

ABSTRACT Herpes zoster (HZ) poses a significant health burden on older adults, for whom vaccination (HZV) is the most effective preventive strategy. Despite this, HZV coverage in China remains critically low. This study aimed to identify key determinants of HZV uptake and willingness among urban Chinese older adults using both traditional and machine learning methods. A cross-sectional survey was conducted from December 2024 to January 2025 among adults aged ≥60 y in six major Chinese cities. We collected data on sociodemographics, health status, HZV awareness, and vaccination behavior. Chi-square tests, multivariate logistic regression, and a conditional inference tree model were used for analysis. The overall HZV coverage was only 13.7%. Among vaccinated individuals, awareness of eligibility (OR = 5.623, 95% CI: [4.566, 6.924]) and receiving a physicians’ recommendation (OR = 2.342, 95% CI: [1.921, 2.855]) were the most powerful predictors. Other significant factors included regional health insurance policies and educational level (P < .05). For the vast majority who were unvaccinated, high cost was the primary barrier, and willingness to vaccinate was projected to rise to 28.3% if the vaccine were more affordable. HZV coverage among China’s urban elderly is alarmingly low, hindered by distinct barriers for different subgroups. While enhancing physicians’ recommendation and eligibility awareness is crucial for driving uptake, addressing the financial barrier is paramount to unlocking vaccination willingness among the broader unvaccinated population. A multi-faceted public health strategy targeting both informational and economic barriers is urgently needed to improve HZV coverage.

ABSTRACT Achieving equitable access to life-course vaccination is a central objective of the global Immunization Agenda 2030 (IA2030). Ethiopia has made notable gains in routine immunization; however, disparities remain, particularly in underserved, pastoralist, and conflict-affected regions. This study assessed vaccination coverage, disparities, and barriers to service utilization across four regions of Ethiopia. A community-based cross-sectional survey was conducted in 57 woredas (districts) of Afar, Amhara, Oromia, and Tigray Regional states. Trained health workers administered digital questionnaires with GPS-enabled devices to caregivers, and eligible individuals subsequently received vaccines. The study enumerated 1.2 million households comprising 5.3 million individuals, including children under five, adolescent girls (9–14 y), pregnant women, and person aged 12 y and above. Descriptive and geospatial analyses were applied to examine coverage levels and disparities. The findings were revealed that 9.1% were zero dose, and 11.2% under-immunized, with measles-containing vaccine (MCV1) coverage at 88.3% among children aged 12–59 months. In addition, 79.6% of pregnant women were received tetanus-diphtheria (Td) vaccine, 75.3% of adolescent girls received Human Papilloma Virus (HPV) vaccine, while only almost half 53.8% of individuals aged 12 y and above received COVID-19 vaccine. Marked regional disparities were emerged: Afar recorded the highest zero-dose prevalence (24%), whereas Amhara and Tigray reported disparity levels below 10%. Despite progress in routine immunization, inequities persist, disproportionately affecting remote and marginalized populations. Addressing these gaps requires integrating geospatial microplanning, expanding mobile outreach, and applying culturally tailored demand-generation strategies to ensure equitable vaccine access and advance IA2030 targets.

ABSTRACT A multicomponent vaccine against seasonal influenza and COVID-19 could reduce disease burden in adults by providing simultaneous protection in a single-dose regimen. The first-generation, mRNA-based, multicomponent mRNA-1073 vaccine, combining antigens encoded by mRNA-1010 (influenza) and mRNA-1273 (COVID-19) vaccines, was investigated in a phase 1/2 clinical trial. This stratified, observer-blinded study randomly assigned healthy adults (18–75 years) to receive mRNA-1073 (25-µg, 50-µg, or 100-µg) + placebo, mRNA-1273 (50-μg) + placebo, mRNA-1010 (50-μg) + placebo, or co-administered mRNA-1010 (50-μg) + mRNA-1273 (50-μg) on day 1. Primary study objectives were safety and reactogenicity. Secondary study objectives assessed humoral immunogenicity against vaccine-matched influenza and SARS-CoV-2 strains at day 29 and all evaluable time points through day 181. An exploratory objective was to further characterize immune responses across the study vaccines. Overall, 550 participants were randomly assigned to receive study vaccination. mRNA-1073 exhibited dose-dependent reactogenicity. Most solicited adverse reactions were grade 1 or 2 in severity; no grade 4 events, serious adverse events related to study vaccination, or deaths were reported. A single dose of mRNA-1073 elicited durable immune responses through 6 months against all vaccine-matched influenza and SARS-CoV-2 strains. Systems serology analysis indicated that mRNA-1073 induced robust, balanced antibody responses with comparable immune profiles to mRNA-1010 + mRNA-1273. mRNA-1073 had an acceptable safety profile and elicited durable immune responses against all vaccine-matched influenza and SARS-CoV-2 strains, supporting ongoing evaluations of mRNA-based multicomponent vaccines that simultaneously protect against seasonal influenza and COVID-19 in a single dose. Registration: ClinicalTrials.gov identifier: NCT05375838 (https://clinicaltrials.gov/study/NCT05375838).

ABSTRACT The COVID-19 pandemic brought about a unique and rapid period of global vaccine innovation. It revealed structural challenges not only in global vaccine affordability and distribution but in the liability and indemnity structures that can both impede access and affect fair outcomes for the small number of people who suffer severe side effects. This review examines vaccine injury and compensation mechanisms, including no-fault compensation schemes, aimed at addressing both the liability and indemnity concerns of developers and the compensation due those suffering severe side effects. The ultimate aim of the review is to provide a classification of systems for those countries that are considering adopting NFCS as part of their broader public health readiness and preparedness strategies.