Vaccines最新文献

Background/Objectives: The rapid development of safe and efficacious vaccines is often hindered by extensive, mandated non-clinical safety evaluations in animals. With the aim to provide scientific evidence supporting a "vaccine platform approach", here we present the complete non-clinical studies for two investigational vaccines, GRAd-COV2 and GRAdHIVNE1, based on GRAd, a gorilla-derived group C adenoviral vector. Methods: The biodistribution of GRAd genomes following the intramuscular administration of the vaccines was assessed in rats by a sensitive qPCR method. Local tolerance and systemic toxic effects were evaluated in single- and repeated-dose toxicity studies in rabbits. Results: GRAd-COV2 and GRAdHIVNE1 were well-tolerated. Distribution was highly confined to the injection site and draining lymph nodes, and toxicity profile consisted of transient, non-adverse inflammatory responses, while the expected immune responses to the encoded antigens were successfully induced. Notably, both vaccines demonstrated a consistent safety profile despite transgene and backbone differences, comparable to other replication-defective adenoviral vectors. Conclusions: The established non-clinical safety profile of the GRAd platform provides a robust foundation for a more efficient and streamlined regulatory pathway. By leveraging this prior knowledge, future GRAd-based vaccines can achieve accelerated clinical development while fully adhering to the ethical principles of replacement, reduction, and refinement of animal use in research.

The human papillomavirus (HPV) is the leading cause of cervical and oropharyngeal cancers. Vaccination can prevent over 90% of HPV-attributed cancers. Rural populations are less likely to initiate and complete HPV vaccinations than urban. The primary objective of this paper is to systematically examine the multilevel (child/youth, parent/caregiver, physician/team, healthcare organization, community, and policy) influences on HPV vaccine uptake in the rural US population. As a secondary aim, we seek to identify gaps in the research that could contribute to the development of more precise intervention approaches in this population. The study adds to the limited number of recent reviews on rural HPV vaccine uptake in the US.

Method: We conducted a systematic search of published empirical studies over 13 years (2010-2023), resulting in 1657 publications. The following databases were searched: Medline (OVID), Embase, CINAHL, PsychInfo, Cochrane, Sociological Abstracts, and Scopus using pre-specified inclusion criteria. Two reviewers independently coded 101 full texts; discrepancies were resolved by a third reviewer. The primary outcome was HPV vaccine uptake.

Results: Adolescents themselves were the most common foci of change. Barriers to rural HPV uptake included limited; vaccine awareness, access to vaccines for children vaccination sites, and primary care recommendations.

Conclusions: Tailored interventions to rural parents/caregivers could increase uptake of the vaccine. Provider training increases HPV vaccine recommendations; programs should also be targeted to rural school nurses, pharmacists, and dental care providers. Linking primary care practices and public health dissemination strategies are key.

Background/Objectives: Adjuvants, added to vaccines to enhance immune responses, are central to shaping the magnitude and durability of immunity, yet their precise mechanisms remain incompletely defined. This study evaluated how diverse adjuvant combinations influence HPV vaccine immunogenicity in non-human primates, with a particular focus on impacts on hematopoietic biology-megakaryocytes and platelets-and broader innate and adaptive pathways. Methods: Eight adjuvanted formulations, each incorporating distinct immunomodulatory components and delivery platforms, were compared against an alum-only control in non-human primates. Longitudinal antibody titers (HPV16-specific) were measured up to 54 weeks, and blood transcriptomes were profiled at Day 1 and Day 7 after both prime and boost doses to assess pathway-level enrichment and gene-expression patterns. Results: Several adjuvant combinations significantly increased antibody titers at 54 weeks compared with alum alone. Formulations containing cationic lipid or monophosphoryl lipid A (MPL) were associated with enhanced antibody responses. Early upregulation of immune-related genes across innate and adaptive pathways was also observed, with some combinations (e.g., inclusion of QS21 or ISCOMs) showing similar trends. Distinct group- and time-dependent transcriptional signatures were observed, with higher-responding formulations exhibiting stronger enrichment in pathogen-influenced signaling and cellular/humoral immune programs. Conclusions: Adjuvant selection and formulation strategy substantially modulate vaccine immunogenicity and early transcriptional programs, including innate, adaptive, and hematopoietic pathways. While individual adjuvants differentially regulate immune and platelet-associated genes, common pathway-level patterns emerge across formulations. These findings suggest candidate mechanisms for prolonged vaccine efficacy and provide actionable insights to guide rational adjuvant design for sustained immune protection.

Background/Objectives: Vaccination coverage among adolescents remains below the recommended target, highlighting the need for effective educational strategies to improve vaccine knowledge. This study aimed to assess baseline knowledge of vaccines and immune mechanisms among adolescents and to evaluate whether a school-based educational intervention can improve knowledge related to vaccination. Methods: A prospective quasi-experimental pre-post study was conducted between 1 February 2025 and 1 June 2025 among adolescents aged 14-19 years attending high schools in Southern Italy. The intervention was based on the e-Bug educational module and delivered by trained nurses through interactive lessons, gamification, and guided discussions. Vaccine-related knowledge was assessed using a questionnaire administered before and after the intervention. Changes in knowledge scores were analyzed using paired statistical tests, and the effect size was estimated. A stepwise multivariate linear regression model was employed to identify factors associated with post-intervention test scores, with statistical significance set as p ≤ 0.05. Results: Among 386 participants, the majority were female (74.2%), the average age was 15.8, and 15% reported a chronic medical condition. Knowledge gaps were observed at baseline, particularly regarding the items on recommended adolescent vaccinations (37.4%), the definition of innate immunity (25.6%), and the mechanism of vaccines' action (51%). After the intervention, all the items showed an improvement in correct answers, statistically significant for 5 of the 7 analyzed items (r = 0.364, p < 0.001). The most pronounced improvement was in the awareness of age-specific recommended vaccines (61.2%). The multivariate linear regression analysis showed that those with higher pre-intervention test scores, those who had parents with chronic medical conditions, those whose fathers worked, and those willing to participate in similar future interventions were more likely to achieve higher post-intervention test scores. Conclusions: School-based interventions may represent an effective strategy for enhancing adolescents' knowledge related to vaccination, but further studies with control groups and long-term follow-up are needed to confirm effectiveness.

Background: Invasive meningococcal disease (IMD) caused by Neisseria meningitidis remains a major public health concern due to its severity, lethality, and long-term sequelae. To address the rise in serogroups W and Y in Spain, the Community of Madrid implemented a catch-up campaign in 2019-2021, targeting adolescents (ages 13-18) alongside routine tetravalent meningococcus vaccine (MenACWY) at age 12. This study evaluated MenACWY catch-up vaccination uptake in routine practice by describing vaccine coverage, temporal trends, and associated factors in adolescents born between 2001 and 2006. Methods: A population-based cross-sectional study was conducted using data from the Community of Madrid's vaccination registry (SISPAL Vacunas). Vaccination coverage was calculated for adolescents with at least one recorded MenACWY dose from age 10 onwards. Temporal trends were analyzed by birth cohort and calendar time, and multivariable logistic regression models were used to identify factors associated with vaccination uptake. Results: Among 424,059 adolescents, overall vaccination coverage by December 2021 was 63.8%, ranging from 54.4% to 78.2% across birth cohorts. Coverage was highest in the 2006 cohort, likely due to co-administration with the tetanus and diphtheria (Td) booster. A slightly higher uptake was observed among females and adolescents with chronic conditions, while foreign-born adolescents consistently showed lower coverage. COVID-19 disruptions led to temporal variability, with sharp declines during lockdowns and partial recoveries thereafter, with persistent sociodemographic differences in uptake. Conclusions: By December 2021, coverage was incomplete, with marked variability across birth cohorts. Higher uptake was observed when vaccination was integrated into routine visits, while persistent sociodemographic disparities remained evident. These observational findings are consistent with the programmatic value of combined catch-up and routine strategies and the need for targeted actions to ensure equitable MenACWY coverage.

Respiratory infections cause substantial morbidity and mortality in older adults and other at-risk adult populations. Despite the availability of effective vaccines, adult vaccination coverage remains suboptimal. This narrative review examines strategies designed to improve vaccine uptake among non-pregnant adults aged ≥18 years and inform future adult vaccination strategies. We conducted a targeted literature search using keywords for vaccination, respiratory diseases, strategy/program/implementation, and adults in PubMed database and CDC, WHO, and ECDC websites, between 2014 and 2024. A snowball search of literature reviews and key references was also performed to identify additional relevant studies. Eligible publications focused on vaccination strategies against influenza, COVID-19, and pneumococcal disease targeting non-pregnant adults (≥18 years). We categorized the strategies by intervention type to describe their influence on vaccination campaigns and vaccine uptake/coverage. We included 45 publications, encompassing strategies focused on individual decision-making, healthcare system functions, and national policy. Educational and awareness interventions (such as healthcare worker/provider recommendations during consultation, phone calls, letters, text messages, and social media outreach) reportedly raised vaccination rates. Access-related factors, including convenient vaccination sites and free or subsidized vaccines, were reported to be important factors in improving coverage in underserved communities. Within healthcare settings, strategies such as continuous vaccine provider training and workflow/process optimization were shown to enhance vaccination delivery. At the local or national policy levels, legislation governing program targets shaped immunization efforts and facilitated collaborations and partnerships to expand campaign reach. The findings may inform policymakers and public health/immunization practitioners in designing context-specific immunization initiatives that effectively reach adult populations.

Background/objectives: HPV vaccination rates among U.S. young adults remain unchanged at 47% since 2019. Barriers including misinformation, vaccine hesitancy, and stigma surrounding HPV's long-standing association with sexually transmitted infections have limited widespread acceptance among the male population. This experimental study explores how prevention messages incorporating an emotional flow element may influence vaccination intention. It also examines whether vaccination status may differentiate pre-exposure risk-taking tendencies and vaccine perceptions-as well as post-exposure HPV susceptibility, HPV severity, vaccine effectiveness, and emotional response-among young adults.

Methods: A one-factor between-subjects experiment (including facts-only vs. facts→threat vs. facts→threat→hope conditions) was conducted online with a group of Gen Z college students at a U.S. university (N = 440).

Results: ANCOVA results indicated that emotional flow embedded in the three message conditions did not result in significantly different emotional responses (across all participants) or vaccination intention among the unvaccinated participants. Whereas vaccinated participants reported greater perceived vaccine benefits, HPV susceptibility, HPV severity, and vaccine effectiveness, unvaccinated participants exhibited stronger emotional responses toward the facts→threat→hope message instead. Regression results revealed that vaccine perceptions, risk-taking tendencies, HPV susceptibility, and emotional response significantly predicted vaccination intention, in that order. TV advertising was identified as the leading HPV information source, followed by social media advertisements and recommendations from health professionals.

Conclusions: These findings highlight that incorporating emotional flow may enhance message engagement among unvaccinated individuals. HPV campaigns should consider increasing positive vaccine perceptions, alleviating perceived threat of HPV, and eliciting positive emotional response toward vaccination acceptance and adoption.

Background/objectives: Porcine epidemic diarrhea virus (PEDV), particularly the emerging GII genotype, poses a severe threat to the swine industry in affected regions, primarily in Asia. Current vaccines based on classical strains often provide limited cross-protection against these heterogeneous variants, though it should be noted that these vaccines are primarily designed to induce maternal immunity in sows. The objective of this study was to develop a novel inactivated vaccine using an emerging PEDV GIIc variant and evaluate its immunogenicity and cross-protective efficacy against heterologous strains.

Methods: A novel PEDV strain, designated PEDV-HeN2024, was isolated from clinical samples and identified through cell culture, immunofluorescence assay (IFA), genetic sequencing, and phylogenetic analysis. An inactivated vaccine was prepared by emulsifying the purified virus with ISA 201 VG adjuvant (1:1, v/v). Immunogenicity was assessed in piglets by measuring virus-neutralizing antibody titers and PEDV-specific IgG levels. Cross-protective efficacy was evaluated through in vitro neutralization assays and in vivo challenge studies with homologous GIIc and heterologous GIIa and GIIb strains.

Results: The isolated PEDV-HeN2024 strain demonstrated pathogenicity, causing severe diarrhea and 100% mortality in PEDV-naïve neonatal piglets. Sera from vaccinated animals showed potent cross-neutralizing activity against homologous GIIc, as well as heterologous GIIa and GIIb strains. In challenge studies, vaccinated piglets were significantly protected against clinical disease, showing no diarrhea or viral shedding, and maintained normal intestinal architecture.

Conclusions: The inactivated vaccine developed from the emerging PEDV GIIc variant elicits robust humoral immunity and provides cross-protection against prevalent heterologous GII strains. These findings highlight its potential as a promising spectrum vaccine candidate for controlling PEDV outbreaks. This study underscores the importance of using recently circulating strains for vaccine development to overcome the limitations of current vaccines.

Background/Objectives: Persistent human papillomavirus (HPV) infection can lead to malignancies of the cervix, vulva, vagina, penis, anus, and oropharynx. The increasing incidence of HPV-related head and neck cancers has raised concerns regarding potential occupational exposure and transmission risks among healthcare workers. This study aimed to systematically evaluate the evidence on occupational HPV transmission in healthcare settings. Methods: A systematic review of the literature was conducted using three electronic databases (PubMed, Scopus, and Web of Science) from inception to August 2025, following PRISMA 2020 guidelines. A total of 34 studies met the inclusion criteria and were included in the review. Expert opinions and practical recommendations from members of the European Society of Gynaecological Oncology (ESGO) Prevention Committee were included to support interpretation of the results. Results: The available literature on occupational HPV transmission was limited, with a paucity of high-quality studies. Nevertheless, existing data suggest a potential occupational risk, particularly during aerosol or smoke-generating procedures performed for cervical intraepithelial neoplasia or cervical cancer. Several studies reported the detection of HPV DNA in surgical smoke or on instruments used during such procedures, indicating possible exposure among healthcare workers. Conclusions: Although current evidence is insufficient to definitively classify HPV infection as an occupational disease, available data indicate a potential exposure risk for healthcare workers involved in HPV-related procedures. Preventive measures, like personal protective equipment, should be emphasized. HPV vaccination has been recommended by some professional societies for healthcare workers performing gynecological procedures, though further research is needed to evaluate vaccine efficacy beyond the standard age range and its cost-effectiveness in this context.

Background: Children with special healthcare needs (CSHCNs) face persistent barriers to timely immunization in China, but comparative evidence across disease groups and vaccines, and data on immune function, are limited.

Methods: We conducted a retrospective cohort study linking electronic medical records, vaccination records, and a structured telephone and questionnaire follow-up. We estimated timely vaccination by National Immunization Program (NIP) dose definitions, assessed catch-up completion at follow-up, and compared cellular/humoral/complement immune indices with published pediatric reference ranges. Group differences used ANOVA/Kruskal-Wallis and chi-square (χ²)/Fisher's exact tests with Bonferroni correction.

Results: Timely vaccination was lower than the national healthy child benchmarks for all NIP vaccines (all p < 0.001); the Japanese encephalitis virus (JE; 24.0%) and measles-containing vaccine (MCV; 25.9%) had the lowest timely completion. A subset of CSHCNs did not receive recommended catch-up vaccinations, primarily due to persistent caregivers' concern and point of vaccination (POV) staff's hesitancy. Delays clustered in neonatal/perinatal disorders for Bacillus Calmette-Guérin (BCG) and hepatitis B vaccine, dose 1 (HepB1). Catch-up completion was highest for hepatitis B vaccine, dose 3 (HepB3) (86.3%) and BCG (81.8%), and lowest for the diphtheria and tetanus vaccine (DT) (49.4%); MCV2 completion was particularly low in hematological diseases. Immunoglobulin A (IgA) and immunoglobulin G (IgG) concentrations were significantly lower in neonatal/perinatal disorders and infectious disease groups versus neurological and immune disorder groups (p < 0.05). No severe adverse events were reported after catch-up.

Conclusions: CSHCNs in China face substantial barriers to timely NIP immunization. Timeliness and catch-up vary substantially by vaccine and underlying condition; neonatal/perinatal disorders contribute disproportionately to early-life delays. Disease-specific guidance, strengthened POV-specialist clinic coordination, immunological monitoring, and supportive policies could improve the vaccination coverage and effectiveness in this vulnerable population.