tetano
Editor, Senior Moderator
Nat Microbiol. 2019 Aug 12. doi: 10.1038/s41564-019-0522-6. [Epub ahead of print]
[h=1]The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.[/h] Wan H[SUP]1[/SUP], Gao J[SUP]2[/SUP], Yang H[SUP]3[/SUP], Yang S[SUP]4[/SUP], Harvey R[SUP]5[/SUP], Chen YQ[SUP]6[/SUP], Zheng NY[SUP]6[/SUP], Chang J[SUP]3[/SUP], Carney PJ[SUP]3[/SUP], Li X[SUP]2[/SUP], Plant E[SUP]2[/SUP], Jiang L[SUP]2[/SUP], Couzens L[SUP]7[/SUP], Wang C[SUP]2[/SUP], Strohmeier S[SUP]8[/SUP], Wu WW[SUP]9[/SUP], Shen RF[SUP]9[/SUP], Krammer F[SUP]8[/SUP], Cipollo JF[SUP]4[/SUP], Wilson PC[SUP]6[/SUP], Stevens J[SUP]3[/SUP], Wan XF[SUP]10[/SUP], Eichelberger MC[SUP]7[/SUP], Ye Z[SUP]2[/SUP].
[h=3]Author information[/h] 1 Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Hongquan.wan@fda.hhs.gov. 2 Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. 3 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. 4 Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. 5 National Institute for Biological Standards and Control, Potters Bar, UK. 6 Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL, USA. 7 Division of Biological Standards and Quantity Control, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. 8 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9 Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. 10 Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS, USA.
[h=3]Abstract[/h] 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.
PMID: 31406333 DOI: 10.1038/s41564-019-0522-6
[h=1]The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.[/h] Wan H[SUP]1[/SUP], Gao J[SUP]2[/SUP], Yang H[SUP]3[/SUP], Yang S[SUP]4[/SUP], Harvey R[SUP]5[/SUP], Chen YQ[SUP]6[/SUP], Zheng NY[SUP]6[/SUP], Chang J[SUP]3[/SUP], Carney PJ[SUP]3[/SUP], Li X[SUP]2[/SUP], Plant E[SUP]2[/SUP], Jiang L[SUP]2[/SUP], Couzens L[SUP]7[/SUP], Wang C[SUP]2[/SUP], Strohmeier S[SUP]8[/SUP], Wu WW[SUP]9[/SUP], Shen RF[SUP]9[/SUP], Krammer F[SUP]8[/SUP], Cipollo JF[SUP]4[/SUP], Wilson PC[SUP]6[/SUP], Stevens J[SUP]3[/SUP], Wan XF[SUP]10[/SUP], Eichelberger MC[SUP]7[/SUP], Ye Z[SUP]2[/SUP].
[h=3]Author information[/h] 1 Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Hongquan.wan@fda.hhs.gov. 2 Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. 3 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. 4 Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. 5 National Institute for Biological Standards and Control, Potters Bar, UK. 6 Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL, USA. 7 Division of Biological Standards and Quantity Control, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. 8 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9 Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. 10 Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS, USA.
[h=3]Abstract[/h] 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.
PMID: 31406333 DOI: 10.1038/s41564-019-0522-6