Influenza Virus Vaccination Elicits Poorly Adapted B Cell Responses in Elderly Individuals

• Type of Material: Article
• Authors: Carole Henry, University of Chicago; Nai-Ying Zheng, University of Chicago; Min Huang, University of Chicago; Alexandra Cabanov, University of Chicago; Karla Thatcher Rojas, University of Chicago; Kaval Kaur, University of Chicago; Sarah F. Andrews, University of Chicago; Anna-Karin E. Palm, University of Chicago; Yao-Qing Chen, University of Chicago; Yang Li, University of Pennsylvania; Katerina Hoskova, University of Chicago; Henry A. Utset, University of Chicago; Marcos C. Vieira, University of Chicago; Jens Wrammert, Emory University; Rafi Ahmed, Emory University; Jeanne Holden-Wiltse, University of Rochester; David J. Topham, University of Rochester; John J. Treanor, University of Rochester; Hildegund C. Ertl, Wistar Institute Vaccine and Immunotherapy Center; Kenneth E. Schmader, Duke University; Sarah Cobey, University of Chicago; Florian Krammer, Icahn School of Medicine at Mount Sinai; Scott E. Hensley, University of Pennsylvania; Harry Greenberg, Stanford University; Xiao-Song He, Stanford University; Patrick C. Wilson, University of Chicago
• Language: English
• Date: 2019-03-13
• Publisher: Cell Press
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.chom.2019.01.002
• Title of Journal or Parent Work: Cell Host and Microbe
• Volume: 25
• Issue: 3
• Start Page: 357
• End Page: 366
• Grant/Funding Information: S.E.H. was supported by 1R01AI113047, 1R01AI108686 and CEIRS HHSN272201400005C.; K.E.S received support from the NIA, Duke Pepper Older Americans Independence Center, P30AG028716.; This study was supported in part by the National Institute of Allergy and Infectious Disease; National Institutes of Health grant numbers U19AI082724 (P.C.W.), P01AI097092 (P.C.W.), U19AI109946 (P.C.W.), U19AI057266 (P.C.W.), HHSN272201400005C (P.C.W.). H.G. and X-S.H. were supported by AI057229 (Stanford). F.K. was supported by R01 AI117287 and NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) contract HHSN272201400008C.; J.H was supported by UL1TR002001 and CEIRS HHSN272201400005C.; M.C.V and S.C were supported by DP2AI117921, CEIRS HHSN272201400005C and the James S. McDonnell Complex Systems Scholar Award.
• Keywords: HUMAN MONOCLONAL-ANTIBODIES; HYPERMUTATION; Parasitology; Virology; REPERTOIRE; Microbiology; AGE; Science & Technology; GERMINAL-CENTERS; SEASONAL INFLUENZA; EFFICACY; Life Sciences & Biomedicine
• Research Categories: Biology, Parasitology; Biology, Virology; Biology, Microbiology

Abstract

Influenza is a leading cause of death in the elderly, and the vaccine protects only a fraction of this population. A key aspect of antibody-mediated anti-influenza virus immunity is adaptation to antigenically distinct epitopes on emerging strains. We examined factors contributing to reduced influenza vaccine efficacy in the elderly and uncovered a dramatic reduction in the accumulation of de novo immunoglobulin gene somatic mutations upon vaccination. This reduction is associated with a significant decrease in the capacity of antibodies to target the viral glycoprotein, hemagglutinin (HA), and critical protective epitopes surrounding the HA receptor-binding domain. Immune escape by antigenic drift, in which viruses generate mutations in key antigenic epitopes, becomes highly exaggerated. Because of this reduced adaptability, most B cells activated in the elderly cohort target highly conserved but less potent epitopes. Given these findings, vaccines driving immunoglobulin gene somatic hypermutation should be a priority to protect elderly individuals.