A new class of antibodies that overcomes a steric barrier to cross-group neutralization of influenza viruses

• Published in: PLoS biology Vol. 21; no. 12; p. e3002415
• Main Authors: Simmons, Holly C., Watanabe, Akiko, Oguin III, Thomas H., Van Itallie, Elizabeth S., Wiehe, Kevin J., Sempowski, Gregory D., Kuraoka, Masayuki, Kelsoe, Garnett, McCarthy, Kevin R.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.12.2023; Public Library of Science (PLoS)
• Subjects: 60 APPLIED LIFE SCIENCES; Adaptation; Amino acids; Analysis; Antibodies; Antibodies, Viral; Binding Sites; Biology and Life Sciences; Eggs; Enzyme-linked immunoassays; H1N1; Hemagglutinin Glycoproteins, Influenza Virus - chemistry; Hemagglutinins; Humans; Identification and classification; Immunological memory; Influenza; Influenza A Virus, H3N2 Subtype; Influenza Vaccines; Influenza viruses; Influenza, Human; Light; Medicine and Health Sciences; Mutation; Neutralization; Pandemics; Physical Sciences; Properties; Receptors; Research and Analysis Methods; Sialic acids; Vaccines; Viral antibodies; Viral vaccines; Viruses; United States; California; Thailand; United States > US; Phuket Thailand
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3002415

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.