NPJ Vaccines最新文献

Vimkunya, a chikungunya virus (CHIKV) virus-like particle (VLP) vaccine, is well-tolerated and induces a rapid, durable serum neutralizing antibody (SNA) response in individuals aged ≥12 years. This study evaluated the efficacy of human CHIKV VLP antisera to protect cynomolgus macaques from heterologous CHIKV challenge and determined an SNA titer that confers complete protection against viremia. Macaques receiving negative control sera had detectable viremia and RNAemia, whereas those receiving control anti-CHIKV IgG or CHIKV VLP antisera with pre-challenge NT₈₀ ≥ 25.7 had no detectable viremia/RNAemia through 10 days post-challenge. Logistic regression showed that pre-challenge NT₈₀s of 23.6 and 25.9 corresponded with 80% and 90% probability of protection, respectively. Data from seroepidemiology studies demonstrated that a neutralizing titer of >1:10 is protective in convalescent persons. The SNA NT₈₀ threshold of 100 selected by US and European regulators to predict protection against CHIKV disease in humans is conservative by a factor of ~4.

Type I interferons (IFN) are key mediators of innate immune activation, promoting upregulation of costimulatory molecules and Major Histocompatibility Complex (MHC) I/II on antigen-presenting cells (APCs). However, IFN also suppress endogenous translation to restrict viral replication. Critically, IFN-stimulated APCs lose the capacity to acquire new antigens, making the timing of IFN signaling a crucial determinant of vaccine efficacy. Here, we show that both DC-specific loss of IFNα/β receptor (IFNαR) and transient blockade of IFNαR before vaccination enhances vaccine uptake and expression within DCs, improves CD8⁺ T cell priming, and leads to superior tumor control. We also demonstrate that IFN signaling before vaccination, triggered by prior infection or administration of a different vaccine, impairs dendritic cell uptake of mRNA-LNP vaccines and reduces the magnitude of vaccine-specific CD8⁺ T cell responses. These findings highlight the dual-edged nature of IFN signaling and offer a potential strategy for enhancing vaccine-induced immunity.

Hendra (HeV) and Nipah (NiV) are closely related, highly pathogenic paramyxoviruses which cause severe, often fatal disease in humans and animals. There are no approved vaccines to protect humans from HeV or NiV infection, although an ideal vaccine countermeasure should provide a protective immune response against both viruses due to the geographic overlap of the natural bat reservoir and recurrent zoonotic spillover events. Here, we developed a single-cycle, recombinant vesicular stomatitis virus vaccine displaying the HeV (G) glycoprotein (G*rVSV∆G-HeV-G) and performed vaccination, challenge, and passive transfer studies in Syrian golden hamsters. Intramuscular vaccination with a single 1.0E7 PFU dose of G*rVSV∆G-HeV-G uniformly protected from lethal HeV and NiV infection, with neutralizing antibodies elicited by the G*rVSV∆G-HeV-G vaccine identified as a correlate of protection in subsequent passive transfer experiments. Our data indicate that the experimental G*rVSV∆G-HeV-G vaccine is effective in protecting against lethal henipavirus disease in a sensitive animal model.

The disease burden of COVID-19 significantly decreased with the implementation of vaccines. However, SARS-CoV-2 variants that escape vaccine induced immunity continue to emerge and may pose a risk to public health. While vaccine updates are available, it remains uncertain whether they are required for full protection. Here, we antigenically characterized SARS-CoV-2 variants JN.1, KP.2, KP.3.1.1, XEC and LP.8.1 by antigenic cartography and evaluated in vivo protection of JN.1 vaccination in hamsters. Antigenic cartography revealed that these variants are antigenically closely related. In vivo experiments showed that JN.1 vaccination blocked viral replication and inflammation in the lower respiratory tract of JN.1, KP.2 and KP.3.1.1 infected animals. However, despite close antigenic proximity, KP.3.1.1 infected JN.1 vaccinated animals showed evidence of viral replication in the upper respiratory tract, indicative for immune escape. These data demonstrate the strength of combining antigenic cartography with experimental challenge studies to study SARS-CoV-2 immune escape for vaccine updates.

Antibiotics are essential for treating bacterial infections, but the growing problem of antimicrobial resistance (AMR) undermines their effectiveness. Vaccines targeting multidrug-resistant (MDR) bacteria are urgently needed. Here, we developed next-generation mRNA vaccines encoding two novel target antigens: phosphate-specific transport protein (PstS) and DUF3748 domain-containing protein (YidR). The resulting fusion proteins exhibited high expression and secretion in vitro and provided strong protective efficacy in mice against Klebsiella pneumoniae (K. pneumoniae) and enterohemorrhagic Escherichia coli (EHEC), significantly reducing bacterial loads and organ damage. Moreover, the K. pneumoniae-based mRNA vaccine (KV3), encoding the PstS-YidR fusion protein, elicited notable cross-protection against four Enterobacteriaceae species, including K. pneumoniae, EHEC, Salmonella enterica (S. enterica), and Shigella flexneri (S. flexneri). In conclusion, this study demonstrates the potential of mRNA vaccines employing fusion protein containing a novel target antigen to combat MDR Enterobacteriaceae with significant cross-protective effects.

Mycoplasma synoviae (MS) is a significant pathogen mentioned by the World Organisation for Animal Health (WOAH) and has caused substantial economic losses to the global poultry industry. The prevention and control strategies are primarily based on flock purification, antibiotic treatment, and vaccination. Given the high cost and extended timeline of flock purification, along with the growing antibiotic resistance, vaccination remains the most effective strategy for preventing MS transmission. This study employed pangenome analysis combined with reverse vaccinology (RV) to identify protective antigens against MS. At last, three proteins namely VY320 (elongation factor P), VY430 (50S ribosomal protein L6), and VY930 (YbhB/YbcL family Raf kinase inhibitor-like protein), were selected to assess their potential as candidate subunit vaccines. Furthermore, a lesion scoring method using a foot pad challenge model was established to evaluate the protective efficacy of the MS vaccine. The results indicated that the VY930 protein is an effective antigen and can activate strong humoral and cellular immunity responses in immunized flocks, superior to the inactivated vaccine. The screening strategy, evaluation methods, and related findings of this study may provide valuable insights into the prevention and control of MS.

Wild poliovirus remains endemic in Pakistan and Afghanistan despite global progress. We quantified immunity to poliovirus types 1-3 among children aged 6-23 months in 44 high-risk districts (2022-2023) using a cross-sectional serosurvey with probability proportional to size (PPS) cluster sampling. We enrolled 20,680 children (10,112 aged 6-11 months; 10,568 aged 12-23 months). Seroprevalence among 6-11-month-olds was 94.5% (type 1), 44.6% (type 2), and 88.0% (type 3); among 12-23-month-olds, it was 95.9%, 53.8%, and 91.2%, respectively. Type 1 seropositivity was highest across provinces; type 3 exceeded 90% except in Balochistan and KP; type 2 was lowest everywhere. Younger children have lower immunity. In multivariable models, residence in Balochistan predicted reduced seroprotection (AOR 0.178, 95% CI 0.066-0.484); older age (AOR 1.356, 1.161-1.583), full immunization (AOR 2.004, 1.643-2.444); and receiving <4 oral poliovirus vaccine (OPV) doses showed higher odds (AOR 1.25, 1.021-1.529) of seroprotection. Wealth showed a non-linear association. Gaps in types 2-3 warrant stronger routine immunization, expanded inactivated polio vaccine (IPV), and tailored supplementary immunization activities (SIAs).

SARS-CoV-2 immunity and innate immune training may influence influenza vaccine immunogenicity. We investigated this in India. Adult volunteers with hybrid SARS-CoV-2 immunity were administered Fluarix^TM Tetra (GlaxoSmithKlein) 2022/2023 NH Vaccine in 2022. Significant induction of hemagglutinin inhibition-specific antibodies and polyfunctional central memory CD4⁺ T-cells (TCM) were observed 1-week post-vaccination with variable induction of CD8⁺T-cell and innate effectors. Vaccination also expanded Flu-specific regulatory T-cells (Treg), which negatively correlated with CD4 responses, highlighting vaccine immunogenicity may be subject to Treg dampening. Fluarix^TM did not boost SARS-CoV-2 immunity. However, SARS-CoV-2-specific T-cell responses correlated positively with vaccine-induced T-cell responses. We evaluated trained immunity post-COVID-19 as a potential regulatory mechanism linking SARS-CoV-2 and heterologous vaccine immunogenicity. We observed, elevated frequencies of basal bacterial Lipopolysaccharide (LPS)-induced IL-6⁺IL1β⁺HLA-DR⁺CD14⁺CD16^- frequencies post-COVID-19 correlated positively with vaccine-induced Fluarix-specific CD4 T-cell frequencies. Our study highlights a potential positive role for COVID-19-driven immune imprinting on heterologous vaccine immunogenicity in a post-COVID-19 era.

Influenza virus infection poses a significant health risk to newborns, with this population experiencing higher hospitalization and mortality rates compared to older children. The heightened vulnerability of this age group results from a combination of an altered immune system and lack of a licensed vaccine for children under six months of age. mRNA-LNP vaccines have shown remarkable efficacy, including the capacity to induce antibodies in poorly responding populations. This makes them a promising candidate for addressing the unique immunological environment of newborns. Here, we leveraged the close immunological and physiological similarity of NHP to evaluate the efficacy of an influenza hemagglutinin mRNA-LNP vaccine in newborns. Our findings show the HA mRNA-LNP vaccine elicits robust, multi-functional antibody responses in newborn NHP that result in significantly reduced viral load and disease severity following challenge. These results highlight the potential of mRNA-based vaccines as a transformative approach to protect the vulnerable newborn population against influenza. Continued development and optimization of this platform could address the critical gap in influenza virus and other pathogen vaccine coverage for infants under six months of age.