Vaccines最新文献

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the global COVID-19 pandemic, which led to hundreds of millions of human infections and more than seven million deaths worldwide. Major variants of concern, particularly the Omicron variant and its associated subvariants, can escape the vaccines developed so far to target previous strains/subvariants. Therefore, effective vaccines that broadly neutralize different Omicron subvariants and show good protective efficacy are needed to prevent further spread of Omicron. The spike (S) protein, including its receptor-binding domain (RBD), is a key vaccine target. Methods: Here, we designed a unique mRNA vaccine encoding Omicron-KP.3 RBD based on RBD-truncated S protein backbone of an earlier Omicron subvariant EG.5 (KP3 mRNA), and evaluated its stability, immunogenicity, neutralizing activity, and protective efficacy in a mouse model. Results: Our data showed that the nucleoside-modified, lipid nanoparticle-encapsulated mRNA vaccine was stable at various temperatures during the period of detection. In addition, the vaccine elicited potent antibody responses with broadly neutralizing activity against multiple Omicron subvariants, including KP.2, KP.3, XEC, and NB.1.8.1. This mRNA vaccine protected immunized transgenic mice from challenge with SARS-CoV-2 Omicron-KP.3. Immune serum also protected against subsequent virus challenge, with the level of protection associating positively with the serum neutralizing antibody titer. Conclusions: Taken together, the data presented herein suggest that this newly designed mRNA vaccine has potential against current and future Omicron subvariants.

Background/Objectives: Recently, the Herpes Zoster (HZ) vaccination has been introduced, alongside influenza and pneumococcal vaccination, at age 65. Factors influencing adherence to this vaccination and its clinical benefits are not completely understood. The aim of this study was to evaluate factors influencing adherence to HZ vaccination compared to pneumococcal and influenza and to assess its clinical effect in preventing acute vascular events. Methods: A total of 1152 patients (520 males), having a birth cohort from 1952 to 1959 inclusive, was recruited, belonging to the District of Udine (N = 839) and to the ASAPs 2 and 3 of Pordenone (N = 313). For each patient, a form was compiled. Results: HZ vaccination was administered to 498 patients, influenza to 665, and pneumococcal to 742 (p < 0.0001). Among the vaccinated, 266 received the live-attenuated version, and 232 the recombinant HZ vaccine. In logistic regression, the presence of addictions, low educational level, and poor socioeconomic status were strongly associated with lower vaccine adherence. The presence of chronic diseases enhanced only pneumococcal (p < 0.001) and influenza (p < 0.001) vaccine adherence. Forty-two non-fatal acute vascular events were recorded from age 65 onwards: 14 cardiac, 20 cerebrovascular, and 8 peripheric. Only 6/493 patients experienced an event following HZ vaccination compared to 36/659 unvaccinated subjects (p = 0.0003). In Cox modeling, HZ vaccination proved to be an independent predictor in preventing subsequent acute vascular events (p < 0.001). Conclusions: The presence of pathologies does not enhance adherence to HZ vaccination while an unfavorable socio-environmental context greatly hinders it. HZ vaccination, but not influenza and pneumococcal vaccination, appears to protect against the occurrence of acute vascular events.

Background: Feline panleukopenia virus (FPV) causes acute and frequently fatal disease in cats, underscoring the urgent need for safe, rapidly effective, and scalable vaccines. While virus-like particle (VLP) vaccines are inherently safe and immunogenic, their development is constrained by low yields of recombinant protein in insect cell expression systems.

Methods: An optimized baculovirus expression vector system (BEVS) incorporating the hr1-p6.9-p10 transcriptional enhancer and the Ac-ie-01 anti-apoptotic gene was employed to enhance recombinant protein production. VP2 expression levels, viral titers, and hemagglutination activity were quantified using qPCR, SDS-PAGE/Western blotting, transmission electron microscopy (TEM), and functional assays. Immunogenicity and protective efficacy were assessed in both mice and cats through serological analysis, neutralizing antibody detection, and post-challenge clinical monitoring.

Results: The optimized BEVS enhanced recombinant protein transcription by 1.5-fold, viral titers by 3.7-fold, and hemagglutination activity by 15-fold. The purified protein self-assembled into uniform 25 nm virus-like particles (VLPs). Immunization elicited earlier responses compared to commercial vaccines. Vaccinated cats maintained normal body temperature, stable leukocyte counts, and minimal viral shedding following FPV challenge.

Conclusions: This study validates an enhanced BEVS that effectively overcomes VP2 yield constraints and generates highly immunogenic FPV VLPs. The platform enables rapid-onset protection and offers a scalable strategy for next-generation FPV vaccine development.

Background/objectives: Despite large-scale measles and rubella (MR) vaccination campaigns in West Africa, measles outbreaks persist, raising concerns about campaign effectiveness, coverage, and underlying determinants. This study assesses the impact of MR follow-up campaigns in 12 of 17 West African countries (2024-2025) and examines the factors contributing to post-campaign outbreaks. The main objective of this study is to evaluate the impact of MR campaigns on measles transmission, identify the characteristics of post-campaign outbreaks, and propose strategies to improve campaign effectiveness and accelerate progress toward measles elimination in West Africa.

Methods: We conducted a cross-sectional and ecological analytical study to examine spatial and temporal variations based on measles surveillance data from 2024 to 2025, post-campaign coverage surveys (PCCS), district-level outbreak reports, and administrative coverage reports. Trends in measles cases before and after the MMR campaigns were assessed, along with demographic characteristics and spatial analyses of confirmed cases.

Results: In 2024, 70.5% (12/17) of countries conducted measles vaccination campaigns, but measles outbreaks increased in 2025 (64 districts in 2024 versus 383 in 2025). Children under five remained the most affected (54%), with 85% of cases being either unvaccinated (57%) or of unknown status (28%). Administrative coverage exceeded 95% in most countries, but measles PCCS revealed gaps, with only Senegal (93%) and Guinea-Bissau (94%) achieving high verified coverage. No country achieved 95% national MPCC.

Conclusions: Suboptimal campaign quality, gaps in immunity beyond target age groups, and unreliable administrative data contributed to the persistence of outbreaks. Recommendations include extending Measles vaccination campaigns to older children (5-14 years), improving preparedness by drawing on experiences from other programs such as polio, standardizing PCCS data survey and analysis methodologies across all countries, and integrating Measles vaccination campaigns with other services such as nutrition.

Background/Objectives: Healthcare workers (HCW) in primary care settings play a significant role in recommending vaccines to patients. We aimed to describe COVID-19 vaccination knowledge, attitudes, perception, and practices (KAPP) of HCWs in Tunisia and identify associated factors. Methods: We conducted a national cross-sectional survey (29 January to 3 February 2024) among HCWs in primary public healthcare centers using purposive sampling. Factors associated with good knowledge, positive attitude, and good practice, measured through Likert scales using face-to-face questionnaires, were identified using binary logistic regression. Results: We included 906 HCWs (mean age = 41.87 ± 8.89 years). In total, 37.75% (342/906) of HCWs had good knowledge and perception, 4.30% (39/906) had a positive attitude, and 24.9% (226/906) had good practices related to COVID-19 vaccination. Working in urban compared to rural areas was associated with good knowledge (aOR = 1.57, 95%CI = 1.12-2.21) and positive attitude (aOR = 4.94, 95%CI = 1.19-20.44) to COVID-19 vaccination. Physicians had better KAPP scores than other medical professionals. HCWs working in departments with high-risk patients were more likely to have good knowledge (aOR = 1.28, 95%CI = 1.00-1.72). Positive attitude was also associated with being male (aOR = 2.97, 95%CI = 1.75-5.07) and having at least one non-communicable disease (aOR = 1.92, 95%CI = 1.14-3.23). Being male (aOR = 1.97, 95%CI = 1.35-2.88) and having more years of professional experience (aOR = 1.81, 95%CI = 1.29-2.52) were associated with good practice. Conclusions: Just over a third of HCWs in primary healthcare clinics had good knowledge of COVID-19 vaccination, while positive attitudes and good practices were low. Targeted interventions, particularly for HCWs with less professional experience working in rural settings, are needed to increase good practices and improve COVID-19 vaccination coverage in Tunisia.

Background: Despite the availability of a killed whole-virus (KV) vaccine, diarrhea caused by equine rotavirus group A (ERVA) remains a significant health concern for foals in the United States. The vaccine is administered to pregnant mares, with foals protected by passive transfer of colostral antibodies. However, KV-induced immunity is only partially protective and maternal antibody levels in foals are often low and wane rapidly. To address these limitations, we developed a mRNA-based ERVA vaccine encoding the highly conserved VP8* protein to evaluate whether it can provide improved immune protection. Methods: Pregnant mares (n = 12 per group) were immunized either at months 8 and 10 of gestation with the VP8* mRNA or at months 8, 9, and 10 of gestation with the KV. Serum samples were collected from mares before and after immunization and from their foals at ages 1, 35, and 49 days. Serum samples were tested by indirect ELISA for VP8*-specific relative antibody concentrations and relative concentrations were compared for effects of study group and sample-time using linear mixed-effects regression. To detect functional antibodies against ERVA, a virus neutralization titer assay was performed to compare titers between mares vaccinated with the mRNA vaccine (and their foals) and unvaccinated control mares (and their foals). Results: Mares vaccinated with VP8* mRNA had significantly (p < 0.05) higher antibody concentrations after foaling than mares in the KV group, and foals of VP8* mRNA-vaccinated mares had significantly (p < 0.05) higher concentrations through age 49 days than foals in the KV group. In addition, the VP8* mRNA vaccine elicited higher titers of ERVA-neutralizing antibodies against both G3 and G14 strains. Conclusions: Longer-lasting, higher concentrations of virus-neutralizing antibodies might provide superior duration of immunity to ERVA in foals from mares vaccinated with VP8* mRNA.

Background/Objective: The influenza virus remains one of the most prevalent respiratory pathogens, posing significant global health and economic challenges. According to the World Health Organization, the seasonal influenza virus infects up to 1 billion people and causes up to 650,000 deaths, annually. Despite influenza vaccination is the most effective available preventive strategy, its reliance on strain predictions and yearly updates limits its effectiveness. The virus' ability to cause both epidemics and pandemics, driven by zoonotic transmissions, underscores its continuous threat. The ongoing H5N1 avian influenza outbreak is the perfect example, renewing concerns due to its ability to infect over 70 mammalian species and sporadically transmit to humans. This study aims to evaluate the protective potential of two human monoclonal antibodies against diverse and recent influenza virus strains. Method: PN-SIA28 and PN-SIA49 monoclonal antibodies were previously isolated from an individual undergoing seasonal influenza vaccination and with no known recent influenza virus exposure. Their breadth of recognition, neutralization, and conferred in vivo protection were assessed against multiple influenza viruses, including pre-pandemic strains. Structural analyses were performed to characterize antibody-antigen interactions for epitope identification. Results: Both antibodies recognize a broad range of strains and neutralize pre-pandemic avian influenza viruses, including the currently circulating H5N1 clade. Moreover, a structural analysis revealed that PN-SIA49 binds a conserved HA stem region, overlapping with epitopes recognized by other broadly neutralizing antibodies. Conclusions: These findings underscore the potential of broadly neutralizing antibodies as a basis for universal influenza countermeasures against both seasonal and pandemic threats. Additionally, they provide guidance for the design of targeted vaccine strategies to steer immune responses toward broadly protective epitopes.

Background: Solid organ transplant recipients (SOTRs) are highly vulnerable to severe COVID-19 infection, yet initial vaccine trials provided limited data on efficacy and safety in this immunocompromised population. Heterogeneous seroconversion rates and conflicting safety reports complicate the formulation of clear clinical guidelines. This systematic review and meta-analysis aim to aggregate existing evidence to determine the precise seroconversion and safety profiles of COVID-19 vaccines and identify key factors influencing immune response in SOTRs.

Methods: A comprehensive literature search was conducted identifying 125 studies evaluating WHO/FDA-authorized vaccines in SOTRs. Outcomes were the pooled seroconversion proportion and safety profile. Subgroup analyses were performed based on vaccine type, transplanted organ, number of doses, and prior SARS-CoV-2 infection status, confirmed by leave-one-out sensitivity analysis and bootstrap methods.

Results: Most studies assessed mRNA-based vaccines (123/125, 98.4%). The overall pooled seroconversion proportion across all SOTRs was significantly blunted at 0.49 (95% CI, 0.43 to 0.55), demonstrating high heterogeneity (I² = 94.2%). Seroconversion showed a clear positive dose-response relationship, increasing from 27% after one dose to 84% after four doses. Prior COVID-19 infection was the strongest predictor of a response, resulting in a pooled seroconversion of 0.90 (95% CI, 0.82 to 0.94; I² = 0%). Organ-specific analyses revealed the highest response in Liver recipients (0.80) and the lowest in Lung recipients (0.29). Vaccine platform analysis showed that the highest response was with mRNA-1273 (0.55) and the lowest with CoronaVac (0.29). The safety profile was limited.

Conclusions: SOTRs exhibit profound hypo responsiveness to COVID-19 vaccines; however, the extreme heterogeneity observed across studies necessitates a cautious interpretation of pooled seroconversion estimates. While the data indicates a significant dose-response relationship favoring an aggressive, multi-dose strategy, the apparent safety profile may reflect under-reporting and limited follow-up rather than confirmed safety equivalence. Rare but clinically critical outcomes, such as acute allograft rejection, remain inadequately characterized in the current literature. Consequently, while the prioritization of multi-dose regimens and hybrid immunity is supported to maximize protection, clinicians must recognize that individual responses remain highly variable, and the long-term immunological impact of repeated stimulation requires further standardized investigation.

Background: Children and adolescents are pivotal in the transmission of influenza, and vaccination remains the most effective preventive measure. Cell-based influenza vaccines offer advantages over traditional egg-based vaccines by reducing egg-adapted mutations and improving antigenic match. SKYCellflu^® quadrivalent influenza vaccine (QIV; SK bioscience, Korea), the first cell-based QIV licensed in Korea for individuals aged 6 months and older, offers potential advantages; however, its real-world effectiveness in the Korean pediatric population remains limited. Objective: This study aimed to estimate the real-world effectiveness of SKYCellflu^® QIV, a cell-based QIV, in preventing laboratory-confirmed influenza among children and adolescents aged 6 months to 18 years in Korea during the 2024-2025 influenza season. Methods: A multicenter, prospective, test-negative case-control study was conducted from October 2024 to May 2025 across 25 institutions in Korea. Children and adolescents aged 6 months to 18 years who presented within 7 days of the onset of influenza-like illness (fever ≥ 38 °C and at least one respiratory symptom) were enrolled. Influenza infection was confirmed using rapid antigen tests or polymerase chain reaction; participants who tested positive were classified as cases, and those who tested negative for influenza served as controls. All participants were further categorized as vaccinated or unvaccinated based on receipt of SKYCellflu^® QIV. Those who received other influenza vaccines during the season were excluded. Vaccination status was verified through medical records and the national immunization registry. Results: A total of 1476 participants were included (751 cases, 725 controls). The overall adjusted vaccine effectiveness (aVE) was 45.57% (95% CI, 29.38-58.04). The vaccine demonstrated the highest effectiveness in children aged 6-35 months (aVE: 88.55%; 95% CI, 60.39-96.11). Effectiveness was higher against influenza B (aVE: 61.28%; 95% CI, 35.76-76.30) than influenza A (aVE: 41.63%; 95% CI, 22.55-56.01). The vaccine's effectiveness in adolescents was not statistically significant due to the small sample size in this age group. Conclusions: This multicenter test-negative study provides the first real-world effectiveness of SKYCellflu^® QIV in a Korean pediatric population. The results suggest substantial protection in younger children, particularly against influenza B, and support the continued use of annual influenza vaccination in this population. Further studies with larger adolescent cohorts are needed to confirm these findings in older age groups.

Background:Streptococcus pneumoniae is a leading cause of child mortality in Nepal despite the introduction of the 10-valent pneumococcal conjugate vaccine (PCV10). Vaccine effectiveness is threatened by the emergence of non-vaccine serotypes (NVTs) and the multiple serotypes carriage which often fail to be detected by traditional methods. We aimed to study changes in serotype distribution before and after PCV10 immunization among infants, including serotype dominance in Nepalese infants in the post-vaccine era. Methods: We enrolled infants in a longitudinal cohort study (2020-2022) conducted in Bhaktapur, Nepal. Nasopharyngeal swabs were collected before PCV10 dose 1 (6 weeks) and at 9 and 12 months post-immunization. We used a sensitive nanofluidic qPCR platform to detect multiple serotypes and establish their hierarchy by quantifying the bacterial load of each strain. Inverse Probability Weighting (IPW) adjusted risk factor analysis was used to account for loss to follow-up. Results: PCV10 successfully reduced vaccine-type (VT) carriage, declining sharply from 32.8% at 6 weeks to 4.8% at 12 months. VTs were pushed from being the dominant strain to occupying subdominant roles in co-colonization. Conversely, NVTs rapidly filled the vacated niche, showing a significant increase in their dominant status (p < 0.001). The most common replacing NVTs that rose to dominance were 35B, 19A, 6C/6D, and 15B/15C. Significant risk factors for carriage included older infancy (aOR 3.4, 95%CI: 2.6-4.5 at 9 months), a household kitchen in the living area (aOR 1.4, 95%CI: 1.0-1.9), and winter (aOR 1.7, 95%CI: 1.5-2.7) and pre-monsoon seasons (aOR 2.0, 95%CI: 1.5-2.8). Conclusions: While PCV10 reduced overall VT circulation, the persistence of VTs in subdominant niches creates a continuous reservoir for potential re-emergence and antibiotic resistance. This clear hierarchical shift in dominance towards NVTs underscores the urgent need for a public health strategy that includes the adoption of a higher-valent PCV to provide broader protection, and interventions targeting environmental risk factors are essential to sustain long-term reductions in pneumococcal colonization.