Antigenic Drift of the Influenza A(H1N1)pdm09 Virus Neuraminidase Results in Reduced Effectiveness of A/California/7/2009 (H1N1pdm09)-Specific Antibodies

Author:

Gao Jin1,Couzens Laura1,Burke David F.2,Wan Hongquan1,Wilson Patrick3,Memoli Matthew J.4,Xu Xiyan5,Harvey Ruth6,Wrammert Jens7,Ahmed Rafi7,Taubenberger Jeffery K.4,Smith Derek J.2,Fouchier Ron A. M.8,Eichelberger Maryna C.1

Affiliation:

1. Division of Viral Products, Center for Biologics Evaluation and Research, FDA, Silver Spring, Maryland, USA

2. Department of Zoology, University of Cambridge, Cambridge, United Kingdom

3. Department of Medicine, University of Chicago, Chicago, Illinois, USA

4. Laboratory of Infectious Diseases, NIAID, National Institutes of Health, Bethesda, Maryland, USA

5. Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

6. National Institute of Biological Standards and Control, MHRA, South Mimms, United Kingdom

7. Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA

8. Department of Virology, Erasmus Medical Center, Rotterdam, Netherlands

Abstract

The effectiveness of seasonal influenza vaccines against circulating A(H1N1)pdm09 viruses has been modest in recent years, despite the absence of antigenic drift of HA, the primary vaccine component. Human monoclonal antibodies identified antigenic sites in NA that changed early after the new pandemic virus emerged. The reactivity of ferret antisera demonstrated antigenic drift of A(H1N1)pdm09 NA from 2013 onward. Passive transfer of serum raised against A/California/7/2009 was less effective than ferret serum against the homologous virus in protecting mice against a virus with the NA of more recent virus, A/Michigan/45/2015. Given the long-standing observation that NA-inhibiting antibodies are associated with resistance against disease in humans, these data demonstrate the importance of evaluating NA drift and suggest that vaccine effectiveness might be improved by selecting viruses for vaccine production that have NAs antigenically similar to those of circulating influenza viruses.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | U.S. Food and Drug Administration

HHS | Biomedical Advanced Research and Development Authority

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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