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
Lipkin, W. Ian
Del Rio, Carlos
Amara, Rama Rao
Das, Suman Ranjan
O'Donnell, Christopher David
Yewdell, Jon W.
Marasco, Wayne A.
Mulligan, Mark J.
Wilson, Patrick C.
- 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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