Broadly Neutralizing Antibodies Against Conserved Epitopes of the Hemagglutinin Head are Robustly Recalled by a Novel H1N1 Virus

Autor: Julianna Han, Dalia J. Bitar, Siriruk Changrob, Florian Krammer, Sean T. H. Liu, Andrew B. Ward, Henry A. Utset, Lei Li, Alec W. Freyn, Micah E. Tepora, Christopher T. Stamper, Peter Palese, Haley L. Dugan, Patrick C. Wilson, Olivia Stovicek, Natalie J. Hamel, Raffael Nachbagauer, Nai-Ying Zheng, Jenna J. Guthmiller, Min Huang
Rok vydání: 2020
Předmět:
Zdroj: SSRN Electronic Journal.
ISSN: 1556-5068
DOI: 10.2139/ssrn.3736401
Popis: 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.
Databáze: OpenAIRE