@article{86713118709d49b0a775266fbe74e64c,
title = "Polyreactive Broadly Neutralizing B cells Are Selected to Provide Defense against Pandemic Threat Influenza Viruses",
abstract = "Polyreactivity is the ability of a single antibody to bind to multiple molecularly distinct antigens and is a common feature of antibodies induced upon pathogen exposure. However, little is known about the role of polyreactivity during anti-influenza virus antibody responses. By analyzing more than 500 monoclonal antibodies (mAbs) derived from B cells induced by numerous influenza virus vaccines and infections, we found mAbs targeting conserved neutralizing influenza virus hemagglutinin epitopes were polyreactive. Polyreactive mAbs were preferentially induced by novel viral exposures due to their broad viral binding breadth. Polyreactivity augmented mAb viral binding strength by increasing antibody flexibility, allowing for adaption to imperfectly conserved epitopes. Lastly, we found affinity-matured polyreactive B cells were typically derived from germline polyreactive B cells that were preferentially selected to participate in B cell responses over time. Together, our data reveal that polyreactivity is a beneficial feature of antibodies targeting conserved epitopes.",
keywords = "antibody flexibility, broadly neutralizing antibodies, influenza viruses, monoclonal antibodies, polyreactivity",
author = "Guthmiller, {Jenna J.} and Lan, {Linda Yu Ling} and Fern{\'a}ndez-Quintero, {Monica L.} and Julianna Han and Utset, {Henry A.} and Bitar, {Dalia J.} and Hamel, {Natalie J.} and Olivia Stovicek and Lei Li and Micah Tepora and Carole Henry and Neu, {Karlynn E.} and Dugan, {Haley L.} and Borowska, {Marta T.} and Chen, {Yao Qing} and Liu, {Sean T.H.} and Stamper, {Christopher T.} and Zheng, {Nai Ying} and Min Huang and Palm, {Anna Karin E.} and Adolfo Garc{\'i}a-Sastre and Raffael Nachbagauer and Peter Palese and Lynda Coughlan and Florian Krammer and Ward, {Andrew B.} and Liedl, {Klaus R.} and Wilson, {Patrick C.}",
note = "Funding Information: This project was funded in part by the National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health grant numbers U19AI082724 (P.C.W.), U19AI109946 (P.C.W.), U19AI057266 (P.C.W.), P01 AI097092 (P.P.), R01AI145870-01 (P.P.), and T32AI007244-36 (J.H.); and the NIAID Centers of Excellence for Influenza Research and Surveillance ( CEIRS ) grant number HHSN272201400005C (P.C.W.) and HHSN272201400008C (L.C., F.K., A.G.-S., P.P.). This work was also partially supported by the NIAID Collaborative Influenza Vaccine Innovation Centers ( CIVIC ; 75N93019C00051 , F.K., A.G.-S., P.P., A.B.W., P.C.W.). Work related to MD simulations were funded by the Austrian Science Fund grant number P30565 (K.R.L.). We are thankful to the teams at PATH, GlaxoSmithKline, Cincinnati Children{\textquoteright}s Hospital Medical Center, and Duke University for their participation in the chimeric HA vaccine trial NCT03300050 , which was funded by the Bill and Melinda Gates Foundation ( OPP1084518 ). This work is based on research funded in part by the Bill & Melinda Gates Foundation. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Gates Foundation. We thank Sarah Andrews, Jens Wrammert, and Rafi Ahmed for participation in acquiring samples from 2009 MIV and 2010 TIV studies. We thank Erin Adams, Albert Bendelac, Steven Erickson, Christopher Boughter, and Nancy D. Pomarici for fruitful discussion and their support in this project. We also thank Elena Solomaha in the University of Chicago Biophysics Core Facility for her assistance. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = dec,
day = "15",
doi = "10.1016/j.immuni.2020.10.005",
language = "English",
volume = "53",
pages = "1230--1244.e5",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "6",
}