tetano
Editor, Senior Moderator
Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses
1. Andres G. Grandea IIIa,1,
2. Ole A. Olsena,1,
3. Thomas C. Coxa,
4. Mark Renshawa,
5. Philip W. Hammonda,
6. Po-Ying Chan-Huia,
7. Jennifer L. Mitchama,
8. Witold Cieplaka,
9. Shaun M. Stewartb,
10. Michael L. Granthamb,
11. Andrew Pekoszb,
12. Maki Kisoc,
13. Kyoko Shinyad,
14. Masato Hattae,
15. Yoshihiro Kawaokac,d,e,f, and
16. Matthew Moylea,2
1.
aTheraclone Sciences, Seattle, WA, 98104;
2.
bThe W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, 21205;
3.
cDivision of Virology, Department of Microbiology and Immunology, and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku 108-8639, Tokyo, Japan;
4.
dDepartment of Microbiology and Infectious Diseases, Kobe University, Hyogo 650-0017, Japan;
5.
eInfluenza Research Institute, Department of Pathological Sciences, University of Wisconsin-Madison, Madison, WI, 53792; and
6.
fExploratory Research for Advanced Technology Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama 332-0012, Japan
1.
Edited* by Francis V. Chisari, The Scripps Research Institute, La Jolla, CA, and approved June 1, 2010 (received for review October 12, 2009)
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.
http://www.pnas.org/content/early/2010/06/29/0911806107.abstract
1. Andres G. Grandea IIIa,1,
2. Ole A. Olsena,1,
3. Thomas C. Coxa,
4. Mark Renshawa,
5. Philip W. Hammonda,
6. Po-Ying Chan-Huia,
7. Jennifer L. Mitchama,
8. Witold Cieplaka,
9. Shaun M. Stewartb,
10. Michael L. Granthamb,
11. Andrew Pekoszb,
12. Maki Kisoc,
13. Kyoko Shinyad,
14. Masato Hattae,
15. Yoshihiro Kawaokac,d,e,f, and
16. Matthew Moylea,2
1.
aTheraclone Sciences, Seattle, WA, 98104;
2.
bThe W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, 21205;
3.
cDivision of Virology, Department of Microbiology and Immunology, and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku 108-8639, Tokyo, Japan;
4.
dDepartment of Microbiology and Infectious Diseases, Kobe University, Hyogo 650-0017, Japan;
5.
eInfluenza Research Institute, Department of Pathological Sciences, University of Wisconsin-Madison, Madison, WI, 53792; and
6.
fExploratory Research for Advanced Technology Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama 332-0012, Japan
1.
Edited* by Francis V. Chisari, The Scripps Research Institute, La Jolla, CA, and approved June 1, 2010 (received for review October 12, 2009)
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.
http://www.pnas.org/content/early/2010/06/29/0911806107.abstract
