DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain

Journal Article · · Nature Microbiology

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. In this work, 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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE Office of Science (SC); US Food and Drug Administration (FDA); Centers for Disease Control and Prevention (CDC); National Institute of Allergy and Infectious Disease (NIAID); National Institutes of Health (NIH)
Grant/Contract Number:
U19AI082724; U19AI109946; U19AI057266; R01AI116744; HSN272201400008C; HHSN272201400005C
OSTI ID:
1599430
Journal Information:
Nature Microbiology, Vol. 4, Issue 12; ISSN 2058-5276
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 39 works
Citation information provided by
Web of Science

References (45)

Chasing Seasonal Influenza — The Need for a Universal Influenza Vaccine journal January 2018
Influenza Infection in Humans Induces Broadly Cross-Reactive and Protective Neuraminidase-Reactive Antibodies journal April 2018
IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis journal May 2008
Interim Estimates of 2017–18 Seasonal Influenza Vaccine Effectiveness — United States, February 2018 journal February 2018
Influenza Virus: a Master of Metamorphosis journal May 2000
Neuraminidase as an influenza vaccine antigen: a low hanging fruit, ready for picking to improve vaccine effectiveness journal August 2018
Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains journal November 2017
Identification of Hemagglutinin Residues Responsible for H3N2 Antigenic Drift during the 2014–2015 Influenza Season journal July 2015
Antibody to Influenza Virus Neuraminidase: An Independent Correlate of Protection journal April 2015
Early season co-circulation of influenza A(H3N2) and B(Yamagata): interim estimates of 2017/18 vaccine effectiveness, Canada, January 2018 journal February 2018
A structural explanation for the low effectiveness of the seasonal influenza H3N2 vaccine journal October 2017
Randomized comparative study of the serum antihemagglutinin and antineuraminidase antibody responses to six licensed trivalent influenza vaccines journal December 2012
Coot model-building tools for molecular graphics journal November 2004
Use of TLS parameters to model anisotropic displacements in macromolecular refinement journal January 2001
Association of Serum Anti-Neuraminidase Antibody with Resistance to Influenza in Man journal June 1972
A sand fly salivary protein acts as a neutrophil chemoattractant journal May 2021
Influenza Vaccine — Outmaneuvering Antigenic Shift and Drift journal January 2004
Integrated Glycoprotein Immobilization Method for Glycopeptide and Glycan Analysis of Cardiac Hypertrophy journal September 2015
Primary structure of a novel N -glycosidic carboyhydrate unit, derived from hen ovomucoid: A 500-MHz 1 H-NMR study journal February 1983
Effect of Neuraminidase Antibody on hong kong Influenza journal March 1973
Influenza virus neuraminidase (NA): a target for antivirals and vaccines journal June 2016
A practical influenza neutralization assay to simultaneously quantify hemagglutinin and neuraminidase-inhibiting antibody responses journal January 2010
MUSCLE: a multiple sequence alignment method with reduced time and space complexity journal August 2004
Three-dimensional structure of a complex of antibody with influenza virus neuraminidase journal March 1987
Generation of influenza A viruses entirely from cloned cDNAs journal August 1999
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids journal May 2007
Neuraminidase activity provides a practical read-out for a high throughput influenza antiviral screening assay journal January 2008
AntigenMap 3D: an online antigenic cartography resource journal March 2012
2014–2015 Influenza Vaccine Effectiveness in the United States by Vaccine Type journal October 2016
Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence journal June 2004
A Computational Framework for Influenza Antigenic Cartography journal October 2010
Inference of Macromolecular Assemblies from Crystalline State journal September 2007
Comparative Glycomics Analysis of Influenza Hemagglutinin (H5N1) Produced in Vaccine Relevant Cell Platforms journal July 2013
Interim Estimates of 2016–17 Seasonal Influenza Vaccine Effectiveness — United States, February 2017 journal February 2017
An Epidemiologically Significant Epitope of a 1998 Human Influenza Virus Neuraminidase Forms a Highly Hydrated Interface in the NA–Antibody Complex journal February 2006
Evaluation of Antihemagglutinin and Antineuraminidase Antibodies as Correlates of Protection in an Influenza A/H1N1 Virus Healthy Human Challenge Model journal April 2016
Identification of Sialic Acid Linkages on Intact Glycopeptides via Differential Chemical Modification Using IntactGIG-HILIC journal April 2018
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997
Molecular Basis for Broad Neuraminidase Immunity: Conserved Epitopes in Seasonal and Pandemic H1N1 as Well as H5N1 Influenza Viruses journal June 2013
Contacts between Influenza Virus N9 Neuraminidase and Monoclonal Antibody NC10 journal September 2002
A high dosage influenza vaccine induced significantly more neuraminidase antibody than standard vaccine among elderly subjects journal February 2010
Likelihood-enhanced fast translation functions journal March 2005
A novel type of carbohydrate structure present in hen ovomucoid. journal November 1982
Interim estimates of 2017-18 seasonal influenza vaccine effectiveness - United States, February 2018 journal March 2018
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids text January 2007

Figures / Tables (5)