The Scripps Research Institute - Department of Integrative Structural and Computational Biology; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - IAVI Neutralizing Antibody Center
Broadly neutralizing antibodies are critical for protection against drifted and novel influenza viruses. Here, we reveal humans have pre-existing immunity against two broadly neutralizing epitopes of the HA head: the lateral patch and receptor-binding site (RBS). Monoclonal antibodies generated against these epitopes are broadly neutralizing against 40+ years of H1N1 evolution and provide potent protection in vivo. First exposure to the novel 2009 pandemic H1N1 virus recalls memory B cells that target the conserved RBS and lateral patch epitopes. We identified unique repertoire, structural, and binding features of lateral patch and RBS binding antibodies including a lateral patch binding motif shared across subjects. Together, our data indicate that the conserved RBS and lateral patch epitopes are readily targeted by the human memory B cell pool and that universal vaccine strategies should aim to drive antibodies against both conserved head and stalk domain epitopes.
Guthmiller, Jenna J. and Han, Julianna and Li, Lei and Freyn, Alec W. and Liu, Sean T.H. and Stovicek, Olivia and Stamper, Christopher and Dugan, Haley L. and Tepora, Micah E. and Bitar, Dalia J. and Hamel, Natalie J. and Changrob, Siriruk and Zheng, Nai-Ying and Huang, Min and Utset, Henry A. and Krammer, Florian and Nachbagauer, Raffael and Palese, Peter and Ward, Andrew B. and Wilson, Patrick C., Broadly Neutralizing Antibodies Against Conserved Epitopes of the Hemagglutinin Head are Robustly Recalled by a Novel H1N1 Virus. Available at SSRN: https://ssrn.com/abstract=3736401 or http://dx.doi.org/10.2139/ssrn.3736401
This version of the paper has not been formally peer reviewed.
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