tetano
Editor, Senior Moderator
Nat Commun
. 2026 Jan 23.
doi: 10.1038/s41467-026-68457-6. Online ahead of print.
An H5N1 clade 2.3.4.4b virus vaccine that elicits cross-protective antibodies against conserved domains of H5 and N1 glycoproteins
Eduard Puente-Massaguer[SUP] 1 2 [/SUP], Thales Galdino Andrade[SUP] 3 [/SUP], Michael J Scherm[SUP] 1 2 [/SUP], Kirill Vasilev[SUP] 1 2 [/SUP], Hassanein Abozeid[SUP] 4 5 [/SUP], Alesandra J Rodriguez[SUP] 3 [/SUP], Joshua Yueh[SUP] 1 2 [/SUP], Disha Bhavsar[SUP] 1 2 [/SUP], John D Campbell[SUP] 6 [/SUP], Dong Yu[SUP] 6 [/SUP], Richard J Webby[SUP] 7 [/SUP], Yoshihiro Kawaoka[SUP] 4 8 9 10 [/SUP], Gabriele Neumann[SUP] 4 [/SUP], Julianna Han[SUP] 3 [/SUP], Andrew B Ward[SUP] 3 [/SUP], Florian Krammer[SUP] 11 12 13 14 15 [/SUP]
Affiliations
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.
. 2026 Jan 23.
doi: 10.1038/s41467-026-68457-6. Online ahead of print.
An H5N1 clade 2.3.4.4b virus vaccine that elicits cross-protective antibodies against conserved domains of H5 and N1 glycoproteins
Eduard Puente-Massaguer[SUP] 1 2 [/SUP], Thales Galdino Andrade[SUP] 3 [/SUP], Michael J Scherm[SUP] 1 2 [/SUP], Kirill Vasilev[SUP] 1 2 [/SUP], Hassanein Abozeid[SUP] 4 5 [/SUP], Alesandra J Rodriguez[SUP] 3 [/SUP], Joshua Yueh[SUP] 1 2 [/SUP], Disha Bhavsar[SUP] 1 2 [/SUP], John D Campbell[SUP] 6 [/SUP], Dong Yu[SUP] 6 [/SUP], Richard J Webby[SUP] 7 [/SUP], Yoshihiro Kawaoka[SUP] 4 8 9 10 [/SUP], Gabriele Neumann[SUP] 4 [/SUP], Julianna Han[SUP] 3 [/SUP], Andrew B Ward[SUP] 3 [/SUP], Florian Krammer[SUP] 11 12 13 14 15 [/SUP]
Affiliations
- PMID: 41577702
- DOI: 10.1038/s41467-026-68457-6
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.