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Commun Biol . Enhancing the breadth of protection in mice with a multivalent influenza vaccine

tetano

Editor, Senior Moderator
Commun Biol


. 2026 Jan 7.
doi: 10.1038/s42003-025-09451-4. Online ahead of print. Enhancing the breadth of protection in mice with a multivalent influenza vaccine

Xiang Wang[SUP] 1 [/SUP], Yixin Niu[SUP] 1 [/SUP], Ying Hu[SUP] 1 [/SUP], Caihong Zhu[SUP] 1 [/SUP], Xi Yang[SUP] 1 [/SUP], Hongyang Shi[SUP] 2 [/SUP], Yao Yan[SUP] 1 [/SUP], Ping Zhou[SUP] 2 [/SUP], Longfei Ding[SUP] 1 [/SUP], Miaomiao Zhang[SUP] 1 [/SUP], Mangteng Wu[SUP] 3 [/SUP], Shubing Tang[SUP] 4 [/SUP], Man Xing[SUP] 5 [/SUP], Dongming Zhou[SUP] 6 7 [/SUP]



Affiliations
Free article Abstract

The high mutation rate of the influenza virus poses a significant challenge to global health, highlighting the urgent need for broad-spectrum vaccines. Here, we engineered Ad-Hex, a pan-influenza vaccine comprising three chimpanzee adenoviral vectors (Ad-H1H3, Ad-BYBV, and Ad-H5H7), each encoding the hemagglutinin (HA) genes from two distinct influenza virus subtypes/lineages in the △E1 region. A single intranasal dose of Ad-Hex induced robust humoral, cellular, and mucosal immunity, conferring complete protection against lethal challenge with six vaccine-matched strains in female C57BL/6 or Balb/c mice. Notably, the vaccine achieved 60% survival rates against mismatched strains. Mechanistic studies revealed that Ad-Hex activated germinal center B-cell responses not only against the cognate HAs but also against the conserved HA stalks. This drove the production of cross-reactive antibodies, which contributed to heterologous protection along with the CD8[SUP]+[/SUP] T cell response. Our study confirms the feasibility of this multivalent strategy by mixing multiple recombinant adenoviruses and provides insights into the development of multivalent vaccines against other respiratory pathogens.


 
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