@article{aee8684daf0b465bbb5de0c54e0005da,
title = "The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain",
abstract = "A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown. Here, we show that the NA of the circulating A(H3N2) viruses has experienced significant antigenic drift since 2016 compared with the A/Hong Kong/4801/2014 vaccine strain. This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468. As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished. This antigenic drift also reduced NA-antibody-based protection against in vivo virus challenge. X-ray crystallography showed that the glycosylation site at residue 245 is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding. Our findings suggest that NA antigenic drift impacts protection against influenza virus infection, thus highlighting the importance of including NA antigenicity for consideration in the optimization of influenza vaccines.",
author = "Hongquan Wan and Jin Gao and Hua Yang and Shuang Yang and Ruth Harvey and Chen, {Yao Qing} and Zheng, {Nai Ying} and Jessie Chang and Carney, {Paul J.} and Xing Li and Ewan Plant and Lianlian Jiang and Laura Couzens and Carol Wang and Shirin Strohmeier and Wu, {Wells W.} and Shen, {Rong Fong} and Florian Krammer and Cipollo, {John F.} and Wilson, {Patrick C.} and James Stevens and Wan, {Xiu Feng} and Eichelberger, {Maryna C.} and Zhiping Ye",
note = "Funding Information: This work was supported by intramural funds from the Food and Drug Administration and the Centers for Disease Control and Prevention. L.J. was supported by training funds administered by the Oak Ridge Institute for Science and Education. The work was also supported by the National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (grant nos U19AI082724, U19AI109946 and U19AI057266 to P.C.W., and R01AI116744 to X.-F.W.), and the NIAID Centers of Excellence for Influenza Research and Surveillance (grant nos HSN272201400008C to F.K. and HHSN272201400005C to P.C.W.). We thank the St. Jude Children{\textquoteright}s Research Hospital for providing the plasmids that were used to rescue viruses. We thank V. V. Lugovtsev for providing the ferret antisera, L. Li for help with the sequence analysis and L. Qi for help with the statistical analyses. We thank Y. An and A. Cheung for their helpful discussions in this study. We are indebted to the staff of the Division of Veterinary Services, CBER, FDA for the excellent animal care and the Facility for Biotechnology Resources, CBER, FDA for the sequencing work. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Food and Drug Administration and the Centers for Disease Control and Prevention. Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41564-019-0522-6",
language = "English",
volume = "4",
pages = "2216--2225",
journal = "Nature Microbiology",
issn = "2058-5276",
publisher = "Nature Publishing Group",
number = "12",
}