#Preclinical evaluation of an #mRNA #vaccine developed from the first #human isolate of #bovine #H5N1

 

Highlights

• SM102 and DB-Y ionizable lipids deliver H5 mRNA vaccine with high efficiency and safety

• Vaccine-induced antibody and T cell response protect mice from H5N1 challenge

• Pre-existing H1 immunity does not diminish H5-specific immunogenicity

• Vaccine fully protects chicken against clade 2.3.4.4b/h H5 virus challenge

Summary

Given the global threat posed by H5N1 clade 2.3.4.4b avian influenza, rapid development of effective vaccines is imperative. We design an mRNA vaccine encoding hemagglutinin (HA) from A/Texas/37/2024, the first bovine-to-human strain. In murine models, both wild-type and cleavage-site-modified HA vaccines elicit robust and durable humoral immunity, along with a balanced Th1/Th2 response, conferring complete protection against lethal homologous viral challenge. The vaccine, along with the World Health Organization (WHO)-recommended candidate (A/Astrakhan/3212/2020), elicits cross-clade binding antibody responses and demonstrates improvement against specific clades at a 1 μg dose. Pre-existing H1 immunity does not diminish H5-specific immunogenicity. In avian species, the vaccine also provides full protection against lethal clades (2.3.4.4b and 2.3.4.4h). Formulated with another ionizable lipid, the vaccine elicits responses comparable to benchmark lipid nanoparticles (LNPs) and shows a favorable safety profile in rats. This work establishes a rapidly adaptable mRNA-LNP vaccine prototype for pandemic preparedness against evolving avian influenza threats.

Source: 

Link: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(26)00119-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2666379126001199%3Fshowall%3Dtrue

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