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Identification of Antibodies Targeting the H3N2 Hemagglutinin Receptor Binding Site following Vaccination of Humans.


ABSTRACT: Antibodies targeting the receptor binding site (RBS) of the influenza virus hemagglutinin (HA) protein are usually not broadly reactive because their footprints are typically large and extend to nearby variable HA residues. Here, we identify several human H3N2 HA RBS-targeting monoclonal antibodies (mAbs) that are sensitive to substitutions in conventional antigenic sites and are therefore not broadly reactive. However, we also identify an H3N2 HA RBS-targeting mAb that is exceptionally broadly reactive despite being sensitive to substitutions in residues outside of the RBS. We show that similar antibodies are present at measurable levels in the sera of some individuals but that they are inefficiently elicited by conventional vaccines. Our data indicate that HA RBS-targeting antibodies can be effective against variable viral strains even when they are somewhat sensitive to substitutions in HA residues adjacent to the RBS.

SUBMITTER: Zost SJ 

PROVIDER: S-EPMC6953393 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Identification of Antibodies Targeting the H3N2 Hemagglutinin Receptor Binding Site following Vaccination of Humans.

Zost Seth J SJ   Lee Juhye J   Gumina Megan E ME   Parkhouse Kaela K   Henry Carole C   Wu Nicholas C NC   Lee Chang-Chun D CD   Wilson Ian A IA   Wilson Patrick C PC   Bloom Jesse D JD   Hensley Scott E SE  

Cell reports 20191201 13


Antibodies targeting the receptor binding site (RBS) of the influenza virus hemagglutinin (HA) protein are usually not broadly reactive because their footprints are typically large and extend to nearby variable HA residues. Here, we identify several human H3N2 HA RBS-targeting monoclonal antibodies (mAbs) that are sensitive to substitutions in conventional antigenic sites and are therefore not broadly reactive. However, we also identify an H3N2 HA RBS-targeting mAb that is exceptionally broadly  ...[more]

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