Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection |
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Authors: | 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 |
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Affiliation: | Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322, USA. |
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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. |
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