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NPJ Vaccines . Development of a broad-spectrum subunit vaccine against H9N2 avian influenza using HA stem domain scaffold and snoopligase system

tetano

Editor, Senior Moderator
NPJ Vaccines


. 2025 Jul 1;10(1):136.
doi: 10.1038/s41541-025-01191-0. Development of a broad-spectrum subunit vaccine against H9N2 avian influenza using HA stem domain scaffold and snoopligase system

Keji Quan[SUP] #[/SUP][SUP] 1 [/SUP], Nan Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Mengqi Lin[SUP] 1 [/SUP], Yuan Liu[SUP] 1 [/SUP], Yue Li[SUP] 1 [/SUP], Qun Hu[SUP] 1 [/SUP], Maoshun Nie[SUP] 1 [/SUP], Tao Qin[SUP] 1 2 3 4 [/SUP], Sujuan Chen[SUP] 5 6 7 8 [/SUP], Daxin Peng[SUP] 9 10 11 12 [/SUP], Xiufan Liu[SUP] 1 2 3 4 [/SUP]



Affiliations
Abstract

H9N2 avian influenza virus (AIV) is a globally prevalent pathogen that causes economic losses in poultry and poses zoonotic threats. Due to antigenic drift and shift, traditional inactivated vaccines often show reduced efficacy. This study presents a novel subunit vaccine based on a conserved HA6 scaffold derived from the hemagglutinin stem domain and coupled with a fusion peptide epitope (fPE) via Snoopligase-mediated ligation. The HA6 protein was validated by its binding to the broad-spectrum antibody CR6261, and the fPE-HA6 fusion construct incorporated T- and B-cell epitopes. Immunization trials in a chicken demonstrated that fPE-HA6 induced stronger humoral and cellular immune responses than individual immunogens. Upon challenge with H9N2 strains YZ4 and SN, the fusion vaccine significantly reduced viral shedding, demonstrating broad-spectrum protection. These findings highlight the potential of HA6 as a modular scaffold for influenza vaccines and the utility of Snoopligase technology in developing broadly protective immunogens against antigenically variable viruses.


 
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