Generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistance mutations against it

Wei Wang; Russell Vassell; Hyo Sook Song; Qiong Chen; Paul W Keller; Swati Verma; Esmeralda Alvarado-Facundo; Hongquan Wan; Falko Schmeisser; Clement A Meseda; Jerry P Weir; Carol D Weiss

doi:10.1371/journal.pone.0222436

Generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistance mutations against it

PLoS One. 2019 Sep 12;14(9):e0222436. doi: 10.1371/journal.pone.0222436. eCollection 2019.

Affiliation

¹ Division of Viral Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, United States of America.

Abstract

Vaccines that elicit broadly cross-neutralizing antibodies, including antibodies that target the conserved stem of hemagglutinin (HA), are being developed as a strategy for next-generation influenza vaccines that protect against influenza across multiple years. However, efficient induction of cross-neutralizing antibodies remains a challenge, and potential escape mutations have not been well characterized. Here we elicited cross-neutralizing antibodies by immunizing animals with the hemagglutinins from H5 and H9 subtype influenza A viruses that are sensitive to neutralization by stem antibodies. We further isolated and characterized an HA stem monoclonal antibody 4C2 that broadly neutralizes group 1 influenza viruses and identified HA mutations that reduced sensitivity to stem antibodies. Our results offer insights for next-generation influenza vaccine strategies for inducing cross-neutralizing antibodies.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Antibodies, Monoclonal / immunology*
Antibodies, Monoclonal / isolation & purification
Antibodies, Monoclonal / metabolism
Antibodies, Neutralizing / immunology
Antibodies, Viral / immunology
HEK293 Cells
Hemagglutinin Glycoproteins, Influenza Virus / immunology*
Hemagglutinin Glycoproteins, Influenza Virus / metabolism
Hemagglutinins
Humans
Influenza A Virus, H5N1 Subtype / immunology
Influenza A virus / immunology
Influenza Vaccines / immunology*
Influenza, Human / prevention & control
Mice
Neutralization Tests
Orthomyxoviridae Infections / immunology

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Hemagglutinin Glycoproteins, Influenza Virus
Hemagglutinins
Influenza Vaccines

Grants and funding

This work was supported by institutional research funds from the US Food and Drug Administration to CDW. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.