Giuseppe
Emeritus
Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection (JEM, abstract, edited)
[Source: Journal of Experimental Medicine, full text: <cite cite="http://jem.rupress.org/content/early/2011/01/06/jem.20101352">Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection ? JEM</cite>. Abstract, edited.]
Published January 10, 2011
The Rockefeller University Press, doi: 10.1084/jem.20101352
? 2011 Wrammert et al.
Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection
1. Jens Wrammert 1,2, 2. Dimitrios Koutsonanos 2, 3. Gui-Mei Li 1,2, 4. Srilatha Edupuganti 4,5, 5. Jianhua Sui 6, 6. Michael Morrissey 8, 7. Megan McCausland 1,2, 8. Ioanna Skountzou 2, 9. Mady Hornig 9, 10. W. Ian Lipkin 9, 11. Aneesh Mehta 3, 12. Behzad Razavi 5, 13. Carlos Del Rio 3,4,10, 14. Nai-Ying Zheng 8, 15. Jane-Hwei Lee 8, 16. Min Huang 8, 17. Zahida Ali 8, 18. Kaval Kaur 8, 19. Sarah Andrews 8, 20. Rama Rao Amara 1,2, 21. Youliang Wang 1, 22. Suman Ranjan Das 11, 23. Christopher David O'Donnell 12, 24. Jon W. Yewdell 11, 25. Kanta Subbarao 12, 26. Wayne A. Marasco 6, 27. Mark J. Mulligan 4, 28. Richard Compans 1, 29. Rafi Ahmed 1,2, and 30. Patrick C. Wilson 8
Author Affiliations:
1. 1 Emory Vaccine Center,
2 Department of Microbiology and Immunology,
3 Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322
2. 4 Hope Clinic of the Emory Vaccine Center, School of Medicine, Division of Infectious Disease, Decatur, Georgia, 30030
3. 5 Department of Internal Medicine, Emory University, Atlanta, GA 30322
4. 6 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute
5. 7 Department of Medicine, Harvard Medical School, Boston, MA 02115
6. 8 Department of Medicine, Section of Rheumatology, The Committee on Immunology, The Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637
7. 9 Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, NY 10032
8. 10 Hubert Department of Global Health, Rollins School of Public Health and Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322
9. 11 Laboratory of Viral Diseases,
12 Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892
1. CORRESPONDENCE Rafi Ahmed: rahmed@emory.edu OR Patrick C. Wilson: wilsonp@uchicago.edu
Abstract
The 2009 pandemic H1N1 influenza pandemic demonstrated the global health threat of reassortant influenza strains. Herein, we report a detailed analysis of plasmablast and monoclonal antibody responses induced by pandemic H1N1 infection in humans. Unlike antibodies elicited by annual influenza vaccinations, most neutralizing antibodies induced by pandemic H1N1 infection were broadly cross-reactive against epitopes in the hemagglutinin (HA) stalk and head domain of multiple influenza strains. The antibodies were from cells that had undergone extensive affinity maturation. Based on these observations, we postulate that the plasmablasts producing these broadly neutralizing antibodies were predominantly derived from activated memory B cells specific for epitopes conserved in several influenza strains. Consequently, most neutralizing antibodies were broadly reactive against divergent H1N1 and H5N1 influenza strains. This suggests that a pan-influenza vaccine may be possible, given the right immunogen. Antibodies generated potently protected and rescued mice from lethal challenge with pandemic H1N1 or antigenically distinct influenza strains, making them excellent therapeutic candidates.
Footnotes
* Abbreviations used: GC germinal center - HA hemagglutinin - HAI hemagglutinin inhibition - MN microneutralization - TCID50 50% tissue culture infectious dose
* Submitted: 6 July 2010
* Accepted: 13 December 2010
This article is distributed under the terms of an Attribution?Noncommercial?Share Alike?No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution?Noncommercial?Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
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[Source: Journal of Experimental Medicine, full text: <cite cite="http://jem.rupress.org/content/early/2011/01/06/jem.20101352">Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection ? JEM</cite>. Abstract, edited.]
Published January 10, 2011
The Rockefeller University Press, doi: 10.1084/jem.20101352
? 2011 Wrammert et al.
Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection
1. Jens Wrammert 1,2, 2. Dimitrios Koutsonanos 2, 3. Gui-Mei Li 1,2, 4. Srilatha Edupuganti 4,5, 5. Jianhua Sui 6, 6. Michael Morrissey 8, 7. Megan McCausland 1,2, 8. Ioanna Skountzou 2, 9. Mady Hornig 9, 10. W. Ian Lipkin 9, 11. Aneesh Mehta 3, 12. Behzad Razavi 5, 13. Carlos Del Rio 3,4,10, 14. Nai-Ying Zheng 8, 15. Jane-Hwei Lee 8, 16. Min Huang 8, 17. Zahida Ali 8, 18. Kaval Kaur 8, 19. Sarah Andrews 8, 20. Rama Rao Amara 1,2, 21. Youliang Wang 1, 22. Suman Ranjan Das 11, 23. Christopher David O'Donnell 12, 24. Jon W. Yewdell 11, 25. Kanta Subbarao 12, 26. Wayne A. Marasco 6, 27. Mark J. Mulligan 4, 28. Richard Compans 1, 29. Rafi Ahmed 1,2, and 30. Patrick C. Wilson 8
Author Affiliations:
1. 1 Emory Vaccine Center,
2 Department of Microbiology and Immunology,
3 Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322
2. 4 Hope Clinic of the Emory Vaccine Center, School of Medicine, Division of Infectious Disease, Decatur, Georgia, 30030
3. 5 Department of Internal Medicine, Emory University, Atlanta, GA 30322
4. 6 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute
5. 7 Department of Medicine, Harvard Medical School, Boston, MA 02115
6. 8 Department of Medicine, Section of Rheumatology, The Committee on Immunology, The Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637
7. 9 Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, NY 10032
8. 10 Hubert Department of Global Health, Rollins School of Public Health and Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322
9. 11 Laboratory of Viral Diseases,
12 Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892
1. CORRESPONDENCE Rafi Ahmed: rahmed@emory.edu OR Patrick C. Wilson: wilsonp@uchicago.edu
Abstract
The 2009 pandemic H1N1 influenza pandemic demonstrated the global health threat of reassortant influenza strains. Herein, we report a detailed analysis of plasmablast and monoclonal antibody responses induced by pandemic H1N1 infection in humans. Unlike antibodies elicited by annual influenza vaccinations, most neutralizing antibodies induced by pandemic H1N1 infection were broadly cross-reactive against epitopes in the hemagglutinin (HA) stalk and head domain of multiple influenza strains. The antibodies were from cells that had undergone extensive affinity maturation. Based on these observations, we postulate that the plasmablasts producing these broadly neutralizing antibodies were predominantly derived from activated memory B cells specific for epitopes conserved in several influenza strains. Consequently, most neutralizing antibodies were broadly reactive against divergent H1N1 and H5N1 influenza strains. This suggests that a pan-influenza vaccine may be possible, given the right immunogen. Antibodies generated potently protected and rescued mice from lethal challenge with pandemic H1N1 or antigenically distinct influenza strains, making them excellent therapeutic candidates.
Footnotes
* Abbreviations used: GC germinal center - HA hemagglutinin - HAI hemagglutinin inhibition - MN microneutralization - TCID50 50% tissue culture infectious dose
* Submitted: 6 July 2010
* Accepted: 13 December 2010
This article is distributed under the terms of an Attribution?Noncommercial?Share Alike?No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution?Noncommercial?Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
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