NPJ Vaccines最新文献

Autogenous vaccines are increasingly used to control poultry diseases not adequately managed by licensed vaccines. Tailored to flock-specific pathogens, they can improve performance by reducing mortality and morbidity during outbreaks and lowering antimicrobial use in herds with recurrent bacterial challenges. Their value extends to variant viral agents affected by antigenic drift. Despite benefits, variability in efficacy and limited standardized safety data remain challenges for broader adoption.

Chikungunya virus (CHIKV) causes periodic outbreaks and is endemic in more than 110 countries. VIMKUNYA, a CHIKV virus-like particle (CHIKV VLP) vaccine, was recently approved by regulators in the United States, European Union, and United Kingdom. Efficacy of VIMKUNYA in endemic settings is difficult to evaluate due to outbreak unpredictability. We used cynomolgus macaques, which model human CHIKV viremia and disease, to assess CHIKV VLP vaccine efficacy. Doses as low as 1.25 μg of CHIKV VLP with aluminum hydroxide adjuvant and passively transferred IgG from vaccinated humans significantly reduced viremia, disease, and joint pathology. Animals that received IgG doses resulting in mean reciprocal 80% neutralization titers of 35, well below the predicted protective threshold of ≥100, exhibited improved clinical outcomes compared with CHIKV-infected control animals, suggesting clinical benefits may occur at lower antibody levels. These findings demonstrate immunogenicity and protective efficacy of CHIKV VLP and relevance of neutralizing antibodies in protection, reinforcing its use in humans to protect against chikungunya disease.

Self-replicating RNA vaccines delivered by viral replicon particles (VRPs) induce strong immunity, but repeated dosing on short intervals may be limited by vector responses. In patient samples and mice, VRP-srRNA vaccination generated VRP-neutralizing antibodies and T-cell responses to replicase. In mice, a third dose at two-week intervals minimally boosted transgene immunity, and prior VRP exposure reduced responses to a different-transgene VRP. Optimized schedules or heterologous prime-boost may sustain immunogenicity.

The development of an effective vaccine against Helicobacter pylori remains a major global health priority, aimed at reducing infection prevalence and preventing diseases such as chronic gastritis, peptic ulcers, and gastric cancer. Despite extensive research, no vaccine has yet demonstrated durable efficacy in clinical settings. This study describes the development of a novel multi-epitope vaccine targeting H. pylori. Sixteen B- and T-cell epitopes derived from six virulence factors were identified using bioinformatics tools and assembled into a Multi-Epitope Unit (MEU) antigen. The MEU antigen was formulated either as a flagellin-adjuvanted protein or delivered via a recombinant Modified Vaccinia virus Ankara (MVA) viral vector. Vaccine immunogenicity and efficacy were assessed in H. pylori SS1-challenged mice. Both formulations induced robust MEU-specific antibody and CD4⁺ T-cell responses, with the strongest immune responses observed following MEU-flagellin priming combined with MVA-MEU. The vaccines elicited balanced Th1/Th2 immunity and increased CD4⁺NKT-like cells frequencies. Notably, heterologous prime-boost vaccination or two doses of the MVA-MEU achieved complete bacterial clearance in both prophylactic and therapeutic models. These findings support the potential of MEU-based vaccines for preventing and treating H. pylori infection, thereby providing a strong rationale for advancement into toxicology studies clinical development.

Respiratory syncytial virus (RSV) is the leading global cause of serious respiratory disease in infants and an important respiratory pathogen in older adults. The RSV prefusion F protein (preF) is a major target of neutralizing antibodies shown to protect against RSV disease. The bivalent preF protein subunit vaccine (RSVpreF; Abrysvo®) contains stabilized preF antigens representing the two major RSV subgroups, RSV A and RSV B. Here, we characterized the neutralizing activity of adult RSVpreF immune sera against a panel of 65 contemporary, globally circulating RSV A and RSV B clinical isolates, containing various amino acid substitutions across the five major antigenic sites of RSV F (Ø, I, II, III, V). Monoclonal Ab-resistant mutant strains (MARMs) displaying in vitro resistance to nirsevimab, clesrovimab, and palivizumab (up to 300,000-fold resistance over the parental strain) were also evaluated. RSVpreF immune sera effectively neutralized both the panel of global clinical isolates and all MARMs tested. These findings demonstrate that the bivalent RSVpreF polyclonal response maintains robust neutralizing activity against circulating RSV A and B strains, including those that escape RSV F mAbs, and provides broad protective immunity against RSV.

The 24th International Pathogenic Neisseria Conference (IPNC) marked a shift toward a balanced forum addressing both meningococcal and gonococcal disease. This drove discussion on how multivalent meningococcal vaccines are enabling the WHO roadmap to defeat meningitis by 2030, while highlighting growing evidence that effective gonococcal vaccines are achievable. Major challenges remain, including antimicrobial resistance, limited genomic surveillance and incomplete understanding of pathogenesis and immune evasion. These reflections shaped this perspective piece.

Salmonella enterica serovar Enteritidis (S. Enteritidis) is one of most common Salmonella serovars associated with human illness in the U.S. and worldwide. Surveillance from the U.S. National Antimicrobial Resistance Monitoring System indicates an increase in both chicken and human isolates of S. Enteritidis with decreased susceptibility to ciprofloxacin (DSC), a critical antibiotic prescribed for complicated human salmonellosis infections. S. Enteritidis reduction in chickens is a priority of poultry producers and public health agencies to improve food safety. In the current study, efficacy assessment of a live Salmonella vaccine (BBS 1134) revealed significant reduction of cecal and splenic colonization, and prevention of dissemination to the bone marrow by DSC S. Enteritidis in broiler chickens. Microbiome analysis indicated the cecal microbiota of vaccinated chickens is distinct compared to mock-vaccinated birds. The IDEXX SE Ab X2 Test did not detect antibodies to S. Enteritidis in vaccinated chicken serum, thereby permitting differentiation of infected from vaccinated animals (DIVA). Altogether, the Salmonella vaccine is a DIVA vaccine, afforded cross-protection, and significantly reduced intestinal colonization and dissemination to the spleen and bone marrow by DSC S. Enteritidis in chickens, thereby offering a prospective intervention for animal production to reduce food product contamination and improve food safety.

Population-level introduction of pneumococcal conjugate vaccines (PCVs) has increased non-vaccine serotype invasive pneumococcal disease (IPD) incidence in children. Higher-valency PCVs were developed to address shifting disease-causing serotypes. This systematic review and meta-analysis defines trends in CRM197-based PCV immunogenicity in children < 2 years. We searched five databases-EMBASE, MEDLINE, Web of Science Core Collection, Global Health, and Cochrane Central Register of Controlled Trials. Random-effects meta-analyses were conducted using log-transformed IgG GMCs and logit-transformed seroresponse rates to generate pooled estimates. We included 250 articles from 138 study groups involving 243 study arms. Vaccine immunogenicity varied by serotype, vaccine, schedule and region. Pooled IgG GMCs post-childhood-schedule were lowest for serotype 3-PCV20 (0.84 μg/mL; 95%CI: 0.60-1.17), and highest for 15B-PCV20 (16.00 μg/mL; 95%CI: 12.31-20.80). Post-childhood-schedule seroresponse rates were >95% for all serotypes except 3. IgG responses increased with primary-dose number, and were further enhanced by a booster, although magnitude varied by serotype and vaccine; for PCV20, IgG GMCs after two-primary doses were still below the 0.35 µg/mL threshold for six serotypes. A general downward trend in IgG GMCs was observed with increasing vaccine valency. Regional variation in post-childhood-schedule IgG GMCs was observed, with highest GMCs in the Western Pacific Region.

Effective mucosal vaccines are critical for controlling infectious diseases in poultry, yet limitations in antigen delivery systems hinder their development. Here, we present a transgenic Eimeria tenella platform engineered to express multicopy viral capsid protein 1 (VP1) and viral capsid protein 2 (VP2) antigens of chicken infectious anemia virus (CIAV), a major immunosuppressive pathogen in poultry. Using a quadripartite co-transfection system driven by high-activity promoters, we achieved stable integration and expression of heterologous antigens, confirmed via PCR and Western blotting. Fluorescence-assisted cell sorting increased the proportion of recombinant parasites to >90%. Despite modestly reduced fecundity, the engineered strain (Et-TetVP1VP2) retained immunogenicity and induced robust humoral and cellular immune responses in vivo. Oral immunization of chickens conferred protection, reducing viral load and pathological lesions upon CIAV challenge. This work establishes E. tenella as a promising oral vaccine vector, offering a scalable and cost-effective platform for antigen delivery against avian pathogens, with broader implications for mucosal vaccine design.

Gonorrhoea is a global health concern exacerbated by rising antimicrobial resistance. Retrospective analyses indicate that outer membrane vesicle (OMV) vaccines derived from Neisseria meningitidis (MeNZB, 4CMenB) may offer partial cross-protection against gonococcal infection. This review outlines the influence of gonococcal population biology on coverage, immune responses elicited by 4CMenB, and emerging strategies that offer the prospect of rationally designed vaccines dedicated to the prevention of gonococcal disease.