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An #H5N1 clade 2.3.4.4b virus #vaccine that elicits cross-protective #antibodies against conserved domains of H5 and N1 glycoproteins

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By G.M.

 


Abstract

The continuous evolution and global spread of highly pathogenic avian influenza (HPAI) H5N1 viruses, particularly clade 2.3.4.4b, pose major challenges for pandemic preparedness. This study evaluates a low-dose inactivated split-virus vaccine derived from H5N1 clade 2.3.4.4b, formulated with an Alum/CpG adjuvant, in a preclinical female mouse model. The vaccine induces strong humoral and cellular immunity, generating high titers of cross-reactive antibodies against diverse H5 hemagglutinin (HA) and across different N1 neuraminidase (NA) glycoproteins. The Alum/CpG adjuvant supports substantial antigen dose sparing and promotes a balanced Th1/Th2 profile. Functional assays show potent virus neutralization, neuraminidase inhibition, and antibody-dependent cellular cytotoxicity, alongside robust antigen-specific CD4+ and CD8+ T cell responses, efficient control of lung viral replication, and reduced lung inflammation. Vaccinated mice are fully protected from lethal challenge with both homologous H5N1 clade 2.3.4.4b and heterologous clade 1 viruses, despite low hemagglutination inhibition (HAI) titers. Electron microscopy polyclonal epitope mapping shows serum antibodies recognizing multiple epitopes on homologous HA and NA, with cross-reactivity to conserved epitopes on heterologous proteins, indicating broad recognition. Together, these findings support this vaccine candidate as a promising strategy to provide broad, multifunctional, and durable immunity against current and emerging H5N1 threats.

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Link: https://www.nature.com/articles/s41467-026-68457-6

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