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Outflanking immunodominance to target subdominant broadly neutralizing epitopes

Journal article
Authors Davide Angeletti
I. Kosik
J. J. S. Santos
W. T. Yewdell
C. M. Boudreau
V. V. A. Mallajosyula
M. C. Mankowski
M. Chambers
M. Prabhakaran
H. D. Hickman
A. B. McDermott
G. Alter
J. Chaudhuri
J. W. Yewdell
Published in Proceedings of the National Academy of Sciences of the United States of America
Volume 116
Issue 27
Pages 13474-13479
ISSN 0027-8424
Publication year 2019
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 13474-13479
Language en
Links dx.doi.org/10.1073/pnas.1816300116
Keywords Antibodies, B cell, Hemagglutinin, Immunodominance, Influenza
Subject categories Immunology in the medical area

Abstract

A major obstacle to vaccination against antigenically variable viruses is skewing of antibody responses to variable immunodominant epitopes. For influenza virus hemagglutinin (HA), the immunodominance of the variable head impairs responses to the highly conserved stem. Here, we show that head immunodominance depends on the physical attachment of head to stem. Stem immunogenicity is enhanced by immunizing with stem-only constructs or by increasing local HA concentration in the draining lymph node. Surprisingly, coimmunization of full-length HA and stem alters stem-antibody class switching. Our findings delineate strategies for overcoming immunodominance, with important implications for human vaccination. © 2019 National Academy of Sciences. All rights reserved.

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