Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses.
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.
Grandea
Andres G
AG
Theraclone Sciences, Seattle, WA 98104, USA.
Olsen
Ole A
OA
Cox
Thomas C
TC
Renshaw
Mark
M
Hammond
Philip W
PW
Chan-Hui
Po-Ying
PY
Mitcham
Jennifer L
JL
Cieplak
Witold
W
Stewart
Shaun M
SM
Grantham
Michael L
ML
Pekosz
Andrew
A
Kiso
Maki
M
Shinya
Kyoko
K
Hatta
Masato
M
Kawaoka
Yoshihiro
Y
Moyle
Matthew
M
D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D001717:Birds; D003429:Cross Reactions / Q000235:genetics / Q000276:immunology; D004196:Disease Outbreaks; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology*; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology; D005585:Influenza in Birds / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008969:Molecular Sequence Data
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007252:Influenza Vaccines