
SHORT COMMUNICATION Emergence of Antigenic Variants in Bovine H5N1 Influenza Viruses
Kei Miyakawa, Makoto Ota, Kaori Sano, Fumitaka Momose, Noriko Kishida, Tomoko Arita, Yasushi Suzuki, Masayuki Shirakura, Hideki Asanuma, Shinji Watanabe, Hideki Hasegawa
First published: 14 May 2025
https://doi.org/10.1002/jmv.70394
ABSTRACT
The recent emergence of the H5N1 influenza virus in dairy cattle has raised significant public health concerns. Using a previously established pseudovirus-based neutralization assay, we evaluated the impact of emerging hemagglutinin (HA) mutations on the efficacy of current candidate vaccine viruses (CVVs). Neutralization analysis revealed that the cow-derived H5N1 virus showed up to a 2.2-fold reduction in sensitivity compared to the CVV homologous neutralization titers. Among the 1,453 HA sequences analyzed from cow-derived H5N1 viruses, we identified four major mutations (E2K, D104G, V147M, and S336N) that emerged after the initial isolation, with 134 isolates (9.22%) harboring all four mutations. These multi-mutation variants exhibited up to a 3.3-fold reduction compared with the CVV homologous neutralization titers. Single-mutation analysis demonstrated that the D104G mutation, present in 47.8% of sequences, markedly contributed to antibody escape. Our findings highlight the importance of continued surveillance and antigenic evaluation of emerging variants for pandemic preparedness strategies.