The Journal of Experimental Medicine doi: 10.1084/jem.20101352
Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection
Jens Wrammert1,2, Dimitrios Koutsonanos2, Gui-Mei Li1,2, Srilatha Edupuganti4,5, Jianhua Sui6, Michael Morrissey8, Megan McCausland1,2, Ioanna Skountzou2, Mady Hornig9, W. Ian Lipkin9, Aneesh Mehta3, Behzad Razavi5, Carlos Del Rio3,4,10, Nai-Ying Zheng8, Jane-Hwei Lee8, Min Huang8, Zahida Ali8, Kaval Kaur8, Sarah Andrews8, Rama Rao Amara1,2, Youliang Wang1, Suman Ranjan Das11, Christopher David O'Donnell12, Jon W. Yewdell11, Kanta Subbarao12, Wayne A. Marasco6, Mark J. Mulligan4, Richard Compans1, Rafi Ahmed1,2, and Patrick C. Wilson8
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.
