Journal article
Subdominance and poor intrinsic immunogenicity limit humoral immunity targeting influenza HA stem
HX Tan, S Jegaskanda, JA Juno, R Esterbauer, J Wong, HG Kelly, Y Liu, D Tilmanis, AC Hurt, JW Yewdell, SJ Kent, AK Wheatley
Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2019
DOI: 10.1172/JCI123366
Abstract
Both natural influenza infection and current seasonal influenza vaccines primarily induce neutralizing antibody responses against highly diverse epitopes within the “head” of the viral hemagglutinin (HA) protein. There is increasing interest in redirecting immunity toward the more conserved HA stem or stalk as a means of broadening protective antibody responses. Here we examined HA stem–specific B cell and T follicular helper (Tfh) cell responses in the context of influenza infection and immunization in mouse and monkey models. We found that during infection, the stem domain was immunologically subdominant to the head in terms of serum antibody production and antigen-specific B and Tfh cell ..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
We thank the clinical trial staff and participants and Kathleen Wragg for technical support (Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity). This work was supported by National Health and Medical Research Council (NHMRC) program grant ID1052979 (to SJK) and NHMRC project grant ID1129099 (to AKW). YL and JW are supported by a Melbourne International Research Scholarship and a Melbourne International Fee Remission Scholarship. JAJ is supported by a NHMRC fellowship. The Melbourne WHO Collaborating Centre for Reference Research on Influenza is supported by the Australian Government Department of Health.