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Outflanking immunodominance to target subdominant broadly neutralizing epitopes.

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.

SUBMITTER: Angeletti D

PROVIDER: S-EPMC6612916 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Outflanking immunodominance to target subdominant broadly neutralizing epitopes.

Angeletti Davide D Kosik Ivan I Santos Jefferson J S JJS Yewdell William T WT Boudreau Carolyn M CM Mallajosyula Vamsee V A VVA Mankowski Madeleine C MC Chambers Michael M Prabhakaran Madhu M Hickman Heather D HD McDermott Adrian B AB Alter Galit G Chaudhuri Jayanta J Yewdell Jonathan W JW

Proceedings of the National Academy of Sciences of the United States of America 20190618 27

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 ...[more]

PMID: 31213541

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