| Literature DB >> 31213541 |
Davide Angeletti1,2, Ivan Kosik3, Jefferson J S Santos3, William T Yewdell4, Carolyn M Boudreau5,6, Vamsee V A Mallajosyula7, Madeleine C Mankowski3, Michael Chambers8, Madhu Prabhakaran8, Heather D Hickman9, Adrian B McDermott8, Galit Alter5, Jayanta Chaudhuri4, Jonathan W Yewdell1.
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.Entities:
Keywords: B cell; antibodies; hemagglutinin; immunodominance; influenza
Year: 2019 PMID： 31213541 PMCID： PMC6612916 DOI： 10.1073/pnas.1816300116
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205