Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses

Andres G. Grandea, Ole A. Olsen, Thomas C. Cox, Mark Renshaw, Philip W. Hammond, Po Ying Chan-Hui, Jennifer L. Mitcham, Witold Cieplak, Shaun M. Stewart, Michael L. Grantham, Andrew Pekosz, Maki Kiso, Kyoko Shinya, Masato Hatta, Yoshihiro Kawaoka, Matthew Moyle

Research output: Contribution to journalArticle

Abstract

Influenza remains a serious public health threat throughout the world. Vaccines and antivirals are available that can provide protection from infection. However, new viral strains emerge continuously because of the plasticity of the influenza genome, which necessitates annual reformulation of vaccine antigens, and resistance to antivirals can appear rapidly and become entrenched in circulating virus populations. In addition, the spread of new pandemic strains is difficult to contain because of the time required to engineer and manufacture effective vaccines. Monoclonal antibodies that target highly conserved viral epitopes might offer an alternative protection paradigm. Herein we describe the isolation of a panel of monoclonal antibodies derived from the IgG+ memory B cells of healthy, human subjects that recognize a previously unknown conformational epitope within the ectodomain of the influenza matrix 2 protein, M2e. This antibody binding region is highly conserved in influenza A viruses, being present in nearly all strains detected to date, including highly pathogenic viruses that infect primarily birds and swine, and the current 2009 swine-origin H1N1 pandemic strain (S-OIV). Furthermore, these human anti-M2e monoclonal antibodies protect mice from lethal challenges with either H5N1 or H1N1 influenza viruses. These results suggest that viral M2e can elicit broadly cross-reactive and protective antibodies in humans. Accordingly, recombinant forms of these human antibodies may provide useful therapeutic agents to protect against infection from a broad spectrum of influenza A strains.

Original languageEnglish (US)
Pages (from-to)12658-12663
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number28
DOIs
StatePublished - Jul 13 2010

Fingerprint

Influenza A virus
Human Influenza
Epitopes
Vaccines
Antibodies
Monoclonal Antibodies
Pandemics
Antiviral Agents
Swine
Viruses
H1N1 Subtype Influenza A Virus
Infection
Orthomyxoviridae
Birds
Healthy Volunteers
B-Lymphocytes
Public Health
Immunoglobulin G
Genome
Antigens

Keywords

  • Influenza matrix 2 protein
  • Monoclonal
  • Pandemic

ASJC Scopus subject areas

  • General

Cite this

Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses. / Grandea, Andres G.; Olsen, Ole A.; Cox, Thomas C.; Renshaw, Mark; Hammond, Philip W.; Chan-Hui, Po Ying; Mitcham, Jennifer L.; Cieplak, Witold; Stewart, Shaun M.; Grantham, Michael L.; Pekosz, Andrew; Kiso, Maki; Shinya, Kyoko; Hatta, Masato; Kawaoka, Yoshihiro; Moyle, Matthew.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 28, 13.07.2010, p. 12658-12663.

Research output: Contribution to journalArticle

Grandea, AG, Olsen, OA, Cox, TC, Renshaw, M, Hammond, PW, Chan-Hui, PY, Mitcham, JL, Cieplak, W, Stewart, SM, Grantham, ML, Pekosz, A, Kiso, M, Shinya, K, Hatta, M, Kawaoka, Y & Moyle, M 2010, 'Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 28, pp. 12658-12663. https://doi.org/10.1073/pnas.0911806107
Grandea, Andres G. ; Olsen, Ole A. ; Cox, Thomas C. ; Renshaw, Mark ; Hammond, Philip W. ; Chan-Hui, Po Ying ; Mitcham, Jennifer L. ; Cieplak, Witold ; Stewart, Shaun M. ; Grantham, Michael L. ; Pekosz, Andrew ; Kiso, Maki ; Shinya, Kyoko ; Hatta, Masato ; Kawaoka, Yoshihiro ; Moyle, Matthew. / Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 28. pp. 12658-12663.
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