Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection

Jens Wrammert; Dimitrios Koutsonanos; Gui-Mei Li; Srilatha Edupuganti; Jianhua Sui; Michael Morrissey; Megan McCausland; Ioanna Skountzou; Mady Hornig; W. Ian Lipkin; Aneesh Mehta; Behzad Razavi; Carlos Del Rio; Nai-Ying Zheng; Jane-Hwei Lee; Min Huang; Zahida Ali; Kaval Kaur; Sarah Andrews; Rama Rao Amara; Youliang Wang; Suman Ranjan Das; Christopher David O'Donnell; Jon W. Yewdell; Kanta Subbarao; Wayne A. Marasco; Mark J. Mulligan; Richard Compans; Rafi Ahmed; Patrick C. Wilson

Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection
Wrammert, Jens
Koutsonanos, Dimitrios
Li, Gui-Mei
Edupuganti, Srilatha
Sui, Jianhua
Morrissey, Michael
McCausland, Megan
Skountzou, Ioanna
Hornig, Mady
Lipkin, W. Ian
Mehta, Aneesh
Razavi, Behzad
Del Rio, Carlos
Zheng, Nai-Ying
Lee, Jane-Hwei
Huang, Min
Ali, Zahida
Kaur, Kaval
Andrews, Sarah
Amara, Rama Rao
Wang, Youliang
Das, Suman Ranjan
O'Donnell, Christopher David
Yewdell, Jon W.
Subbarao, Kanta
Marasco, Wayne A.
Mulligan, Mark J.
Compans, Richard
Ahmed, Rafi
Wilson, Patrick C.
Pathology and Cell Biology
Center for Infection and Immunity
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Journal of experimental medicine
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.
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Jens Wrammert, Dimitrios Koutsonanos, Gui-Mei Li, Srilatha Edupuganti, Jianhua Sui, Michael Morrissey, Megan McCausland, Ioanna Skountzou, Mady Hornig, W. Ian Lipkin, Aneesh Mehta, Behzad Razavi, Carlos Del Rio, Nai-Ying Zheng, Jane-Hwei Lee, Min Huang, Zahida Ali, Kaval Kaur, Sarah Andrews, Rama Rao Amara, Youliang Wang, Suman Ranjan Das, Christopher David O'Donnell, Jon W. Yewdell, Kanta Subbarao, Wayne A. Marasco, Mark J. Mulligan, Richard Compans, Rafi Ahmed, Patrick C. Wilson, 2011, Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection, Columbia University Academic Commons, http://hdl.handle.net/10022/AC:P:9803.

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