A New Class of Antibodies That Overcomes a Steric Barrier to Cross-group Neutralization of Influenza Viruses

Overview

Journal PLoS Biol

Specialty Biology

Date 2023 Dec 21

PMID 38127922

Authors

Holly C Simmons

Akiko Watanabe

Thomas H Oguin Iii

Elizabeth S Van Itallie

Kevin J Wiehe

Gregory D Sempowski

Masayuki Kuraoka

Garnett Kelsoe

Kevin R McCarthy

Affiliations

Soon will be listed here.

Abstract

Antibody titers that inhibit the influenza virus hemagglutinin (HA) from engaging its receptor are the accepted correlate of protection from infection. Many potent antibodies with broad, intra-subtype specificity bind HA at the receptor binding site (RBS). One barrier to broad H1-H3 cross-subtype neutralization is an insertion (133a) between positions 133 and 134 on the rim of the H1 HA RBS. We describe here a class of antibodies that overcomes this barrier. These genetically unrestricted antibodies are abundant in the human B cell memory compartment. Analysis of the affinities of selected members of this class for historical H1 and H3 isolates suggest that they were elicited by H3 exposure and broadened or diverted by later exposure(s) to H1 HA. RBS mutations in egg-adapted vaccine strains cause the new H1 specificity of these antibodies to depend on the egg adaptation. The results suggest that suitable immunogens might elicit 133a-independent, H1-H3 cross neutralization by RBS-directed antibodies.

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