NPJ Vaccines最新文献

There is currently no Lyme disease (LD) vaccine available for use in humans. Outer surface protein C (OspC) of the causative agent, Borrelia burgdorferi, is a promising LD vaccine target. However, the extensive genetic variation of OspC poses a challenge in affording broad protection. Here, we developed a monovalent mRNA vaccine encoding OspC type A and a polyvalent vaccine encoding OspC types A, C, I, K, and N. The monovalent vaccine conferred complete protection against homologous challenge in mice, inducing functional OspC-specific antibodies and CD4⁺ T cell responses. The polyvalent formulation elicited antibodies to all encoded OspC types and protected against strains expressing OspC types A, I, and K, but not C or N. Increasing the dose enhanced protection against the OspC type C strain. This study is the first demonstration of an effective OspC-targeted mRNA vaccine and supports the development of OspC-based vaccines for broad LD prevention.

The global spread of highly pathogenic avian influenza A(H5N1) viruses poses a serious pandemic threat. While sustained human-to-human transmission has not occurred, widespread circulation in birds, increased detection in mammals, and occasional human spillovers underscore the need for safe and effective vaccines. We evaluated an H5 mRNA vaccine candidate in ferrets using recent clade 2.3.4.4b A(H5N1) human isolates. Vaccination elicited strong neutralizing antibodies, conferred robust protection against lethal challenge, and significantly reduced viral titers. In a direct contact transmission model, mRNA vaccination decreased virus shedding in inoculated ferrets and reduced onward transmission; it also protected vaccinated contact ferrets from infection following exposure to virus-shedding, unvaccinated ferrets. Additionally, sera from vaccinated animals cross-neutralized clade 2.3.2.1e human viruses to varying degrees, depending on the strain. These findings demonstrate that H5 mRNA vaccination not only protects against disease but also reduces transmission, supporting its potential as a key tool for pandemic preparedness.

Prophylactic human papillomavirus vaccines such as Cervarix® and Gardasil®9 induce robust and sustained antibody responses over time. One driver of such responses is memory B-cells (MBCs), primed during initial HPV-vaccine exposure. As part of the Dose Reduction Immunobridging and Safety Study (DoRIS), MBCs were evaluated in peripheral blood mononuclear cells by enzyme-linked immunosorbent spot assay at baseline and at 5 visits post-first vaccine dose to Month 36 in 930 Tanzanian girls randomly allocated to 3, 2, or 1 doses of either vaccine. Most ( > 90%) participants had detectable MBCs at all time points, with maximum responses by Month 7. Geometric mean frequency HPV-specific MBCs and the proportion responding declined thereafter for both vaccines in the 2 and 3-dose arms. MBC frequencies were lower in single-dose than in 2- and 3-doses recipients at all time points subsequent to Month 1. By Month 36, MBC responses to both vaccines for both HPV16 and 18 were similar across all dosing arms. The clinical significance of the dose response remains to be evaluated; however, the presence of MBCs in the circulation after 3 years with a single vaccine dose is encouraging in terms of generating long-lasting protection with a one-dose vaccination strategy.

The SARS-CoV-2 spike receptor binding domain (RBD) is the major target for neutralising antibodies. However, subdomains like RBD may constrain the availability of CD4 T follicular helper (TFH) cells and impact immunogenicity. We engineered a chimeric trimeric RBD (CTR) glycoprotein, replacing the RBD of HKU-1 spike with SARS-CoV-2 RBD (ancestral WT/Omicron BA.2). This maintains trimerised RBD, while providing CD4 help via the HKU-1 scaffold. In C57BL/6 mice, CTR-BA.2 elicited high anti-BA.2-RBD IgG and neutralising titres, matching native spike responses. Germinal centre B cells were predominantly WT⁺/BA.2⁺ cross-reactive, and TFH predominantly recognised HKU-1 epitopes, demonstrating scaffold-directed help. In macaques, CTR-WT elicited comparable anti-RBD IgG, anti-spike IgG and neutralising responses to native spike, with elevated RBD-specific GC B cells in draining lymph nodes. Macaque TFH responses targeted RBD, NTD/S2 or HKU-1 peptides. This chimeric design overcomes poor RBD immunogenicity by engaging CD4 TFH, maintaining neutralising responses that is non-inferior to native spike.

Nipah virus (NiV) and Hendra virus (HeV), two highly pathogenic Henipaviruses (HNVs), pose a significant public health threat. The attachment glycoprotein (G) plays a crucial role in viral attachment and entry, making it an attractive target for vaccine and therapeutic antibody development. However, the antigenic landscape and neutralization sensitivity of the diverse HNV G proteins remain poorly defined. Here, we systematically characterize 27 monoclonal antibodies (mAbs) elicited by NiV G head (G^H) nanoparticle-immunized mice. Among these, 25 mAbs exhibit neutralizing activity against two major NiV strains, NiV-Malaysia and NiV-Bangladesh, with five mAbs also cross-inhibiting HeV infection. Notably, mAbs from two distinct groups conferred complete protection to hamsters against lethal NiV-Malaysia challenge. Structural analysis of NiV G^H in complex with representative Fabs reveals four non-overlapping epitopes, including two novel antigenic sites and one public protective epitope shared across species. MAbs targeting the novel sites bind to the top or side faces of G protein's β-propeller and inhibit viral infection by blocking either receptor engagement or membrane fusion. MAbs recognizing the public epitope block the receptor binding directly. Our study provides a comprehensive antigenic map of the NiV G^H and offers new insights and opportunities for antibody-based therapies and rational vaccine development.

Avian influenza continues to be a major threat to poultry and public health. This study investigated the efficacy of a bivalent H9N2/H5N2 modified live virus (MLV) vaccine delivered through a sequential aerosol priming and drinking water boosting in chickens. We hypothesized that this vaccination strategy would induce robust protective immunity against both low pathogenic H9N2 and high pathogenic H5N1 avian influenza viruses. The results demonstrated that the bivalent MLV vaccine provided sterilizing immunity against homologous and antigenically drifted H9N2 virus challenges. While anti-H5 antibody responses after MLV vaccination were generally weak, a robust anti-N2 antibody response was observed. Notably, the bivalent MLV prime-boost group demonstrated 90% survival against a high-dose H5N1 HPAI challenge. These findings highlight the potential of this mass vaccination approach, utilizing aerosol delivery complemented by drinking water administration, as a convenient and cost-effective method for avian influenza control, particularly H9N2 and H5N1 HPAI.

Mpox is a significant health concern as an infectious disease. Therefore, understanding the immune response triggered in individuals vaccinated with JYNNEOS and those diagnosed with mpox requires further investigation. In this study, we evaluated neutralizing antibody (nAb) titers and profiles of pro-inflammatory and anti-inflammatory cytokines in JYNNEOS-vaccinated individuals with and without prior exposure to poxvirus, as well as in those who were unvaccinated and diagnosed with mpox. Samples were collected from 23 individuals at multiple time points, before vaccination (D0) and after vaccination (D7, D14, D30, D60, and D150), along with 8 samples from individuals with mpox. We observed a significant increase in nAb titers in naive-vaccinated individuals at D60, followed by a long-term decline at D150. The nAb response was significantly higher in the mpox-diagnosed group compared to the naive-vaccinated group at several time points. However, pre-exposed-vaccinated individuals showed significantly higher nAb titers than those with mpox on D14 and D60. A significant increase in the levels of cytokines IL-6 and IL-8 was detected at D30 in naive-vaccinated individuals. These findings enhance our understanding of the immunogenicity and protective mechanisms induced by JYNNEOS vaccination and highlight a previously unreported pro-inflammatory response as part of the immune repertoire triggered post-vaccination.

To promote self-reliance in vaccine production, a chimeric Newcastle Disease Virus (NDV) based vaccine (NDV-HXP-S) was developed in Bangkok, Thailand, with the support of PATH. The interim results of phase 1 on initial safety and immune responses of five formulations: 1 µg, 3 µg, 10 µg, 1 µg+ CpG, and 3 µg+CpG adjuvant were reported. The 3 µg and 3 µg+CpG formulations were selected to advance into phase 2. The full one-year follow-up of safety and immune responses of the NDV-HXP-S vaccine from a pooled phase 1/2 randomized, double-blind, placebo-controlled trial in vaccine naïve individuals with no prior SARS-CoV-2 infection was reported here. The two-dose NDV-HPX-S primary series was safe and elicited a strong immune response over one year, especially in the 3 µg+CpG and 10 µg groups. The 3 µg+CpG group had a significantly higher geometric mean fold rise (GMFR) than the 3 µg group (57.1 vs 40.0, p = 0.028) 14 days after the second dose.