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  • 标题:Outflanking immunodominance to target subdominant broadly neutralizing epitopes
  • 本地全文:下载
  • 作者:Davide Angeletti ; Davide Angeletti ; Ivan Kosik
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2019
  • 卷号:116
  • 期号:27
  • 页码:13474-13479
  • DOI:10.1073/pnas.1816300116
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要: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.
  • 关键词:influenza ; immunodominance ; B cell ; hemagglutinin ; antibodies
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