NPJ Vaccines最新文献

Norovirus can cause severe and potentially fatal gastroenteritis in infants. Mucosal vaccination of breastfeeding women may promote infant protection by enriching antibody responses in consumed breast milk. Here, we report a double-blind, placebo-controlled phase 1 trial in South Africa (SANCTR: DOH-27-072023-7893) to evaluate a single-dose oral bivalent vaccine against norovirus genotypes GI.1 and GII.4 in post-partum breastfeeding women. Safety and reactogenicity (primary outcome), breast milk and serum norovirus-specific antibodies (primary outcome), and passive transfer of antibodies to infants as measured in infant stool (exploratory outcome) were assessed. The vaccine was safe and well tolerated with similar reports of mild or moderate adverse events between placebo (n = 16) and vaccine groups (5 × 10¹⁰ or 1 × 10¹¹ IU/genotype, n = 30/group). Functional norovirus-specific breast milk and serum antibodies were significantly enriched in vaccinated groups. Norovirus-specific IgA in infant stool increased post-vaccination and positively correlated with breast milk IgA, indicating passive transfer. Thus, oral vaccination of breastfeeding women generates robust mucosal and systemic functional maternal antibodies. Our study presents a promising vaccination strategy to provide mucosal anti-norovirus immunity to infants.

Influenza causes substantial morbidity and mortality worldwide. This randomized, open-label, phase 1 trial (ClinicalTrials.gov, NCT05397223, date of registration: May 31, 2022) compared the immunogenicity of an mRNA-based quadrivalent influenza hemagglutinin (HA) vaccine (mRNA-1010) with a licensed comparator (FLUAD) in adults aged 18-75 years. We evaluated humoral and cellular immune responses using hemagglutination inhibition assays, flow cytometry-based memory B cell (MBC) profiling, and intracellular cytokine staining for T-cell characterization. Both vaccines elicited durable hemagglutination inhibition titers and increased HA-specific MBC responses across four vaccine strains. Compared with FLUAD, mRNA-1010 induced higher frequencies of classical and activated MBCs specific to the H3 HA included in the vaccine, while inducing similar MBC responses to the other strains. mRNA-1010 and FLUAD generated strong HA-specific CD4⁺ T-cell responses; a trend toward higher CD8⁺ T-cell responses was observed in mRNA-1010 recipients compared with FLUAD recipients for two of the four strains. These findings support the potential of the mRNA platform for seasonal influenza vaccination.

We preclinically characterize BNT162b3, a nucleoside-modified mRNA-based coronavirus disease 2019 (COVID-19) vaccine encoding a trimerized, cell surface-tethered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD-foldon), formulated in lipid nanoparticles. Intramuscular immunization with BNT162b3 induced high antigen-specific antibody titers with early seroconversion kinetics in mice and rhesus macaques. One dose of BNT162b3 induced high neutralizing antibody titers against pseudoviruses harboring the spike of the SARS-CoV-2 Wuhan-Hu-1 strain and early variants of concern up to Delta, but lower titers against Omicron, the phylogenetically more distant variant. In mice, a second immunization boosted Omicron neutralizing antibody titers to levels comparable to those of other tested variants. The cellular immune response was T helper 1 cell driven. The cell surface-tethered RBD-foldon was more immunogenic than its soluble counterpart. This study demonstrated the suitability of BNT162b3 as COVID-19 vaccine and supported its evaluation in a phase I/II clinical trial (BNT162-04, NCT04537949).

The emergence and broad circulation of highly pathogenic avian influenza (HPAI) H5N1 virus in wild birds and its spillover into dairy cows with sustained transmission in this species pose a major risk to felines, which are highly susceptible and often succumb to the infection. Here, we developed a novel recombinant hemagglutinin H5-based vaccine and evaluated its safety, immunogenicity, and protective efficacy against HPAI H5N1 virus in domestic cats. Immunization of cats with H5-vaccine candidate elicited robust levels of neutralizing antibodies against H5N1 virus and protection against disease, mortality, and infection upon H5N1 virus challenge. The vaccine-elicited immunity significantly reduced virus shedding and viremia, limiting systemic spread and disease severity in immunized animals. Importantly, beyond protecting susceptible felids, vaccinating cats against the H5N1 virus could also reduce the risk of human exposure - underscoring the One Health impact of implementing such a vaccination strategy in feline populations.

Prostate cancer (PC) treatment is evolving beyond conventional therapies. This review explores mRNA-based vaccines as a promising immunotherapy. We discuss their mechanism of action, advantages in production and safety, and results from early clinical trials (e.g., CV9103/4). Key challenges like antigen selection and the immunosuppressive tumor microenvironment are addressed, alongside advancements in lipid nanoparticle delivery and combinatorial strategies with checkpoint inhibitors to enhance efficacy and usher in personalized PC treatment.

Conventional vaccine risk communication, which emphasizes scientific facts about vaccine or disease risks, often overlooks laypeople's values and fails to increase vaccination acceptance. This study developed and tested a participant-informed, value-embedded narrative intervention to improve vaccination acceptance among Hong Kong parents and adults. Two message types were created: a standard message framing vaccines as a medical technology (Med-Tech) and a naturalness-oriented framing (Immune-Trainer), both incorporated narrative communication and imagination simulation. In Study 1, 631 parents were randomly assigned to control, Med-Tech, or Immune-Trainer groups. The Immune-Trainer group showed more positive affective attitudes, generated more naturalness-related cues, and reported higher intention and uptake of childhood influenza vaccination. Study 2, involving 2261 adults and an additional non-narrative, fact-based-only group, largely replicated these findings except for actual uptake. Immune-Trainer outperformed the fact-based-only messages. Significant effects on vaccination intentions and reported actual uptake were observed for influenza but not for COVID-19 vaccination across both samples.

J paramyxovirus (JPV) is a non-segmented, negative-strand RNA virus in the Jeilongvirus genus of the Paramyxoviridae family. Recently, a recombinant JPV lacking the small hydrophobic protein (SH) gene (rJPV-∆SH) has been used as a viral vector for avian influenza virus H5N1 and HIV vaccine development. However, the rJPV-∆SH vector still causes morbidity and mortality in mice. To further develop this vaccine platform, we generated multiple recombinant JPV (rJPV) mutants and tested their pathogenicity in mice. We found that rJPV lacking the syncytial protein (SP) (rJPV-∆SP), rJPV with both SH and SP genes deleted (rJPV-ΔSHΔSP) and a JPV lacking coding sequences for SH, SP, and the putative X open reading frame (rJPV-∆3) were pathogenic in mice. Incorporating mutations in the L gene that mediate pathogenesis into rJPV-∆3 (rJPV-∆3-LW-L) resulted in a fully attenuated virus in mice. rJPV∆3-LW-L-immunized mice were protected during lethal JPV challenge. Furthermore, intranasally administrated rJPV-∆3-LW-L expressing Nipah virus (NiV) fusion (F) induced anti-NiV-F antibodies in mice and Syrian hamsters, and a single-dose intranasal immunization with rJPV-∆3-NiV-F-LW-L induced complete protection against lethal NiV challenge in the hamster model. Our work has identified a novel intranasal vaccine vector that is fully attenuated in mice and induces protective immunity in animals.

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.