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Outflanking immunodominance to target subdominant broadly neutralizing epitopes.
Angeletti, Davide; Kosik, Ivan; Santos, Jefferson J S; Yewdell, William T; Boudreau, Carolyn M; Mallajosyula, Vamsee V A; Mankowski, Madeleine C; Chambers, Michael; Prabhakaran, Madhu; Hickman, Heather D; McDermott, Adrian B; Alter, Galit; Chaudhuri, Jayanta; Yewdell, Jonathan W.
Affiliation
  • Angeletti D; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; davide.angeletti@gu.se jyewdell@niaid.nih.gov.
  • Kosik I; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, 40530 Gothenburg, Sweden.
  • Santos JJS; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
  • Yewdell WT; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
  • Boudreau CM; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
  • Mallajosyula VVA; Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139.
  • Mankowski MC; PhD Program in Virology, Division of Medical Sciences, Harvard University, Boston, MA 02115.
  • Chambers M; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305.
  • Prabhakaran M; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
  • Hickman HD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
  • McDermott AB; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
  • Alter G; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
  • Chaudhuri J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
  • Yewdell JW; Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139.
Proc Natl Acad Sci U S A ; 116(27): 13474-13479, 2019 07 02.
Article de En | MEDLINE | ID: mdl-31213541
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.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Virus de la grippe A / Vaccins antigrippaux / Épitopes immunodominants / Anticorps neutralisants / Hémagglutinines / Épitopes Limites: Animals Langue: En Journal: Proc Natl Acad Sci U S A Année: 2019 Type de document: Article
Texte intégral
Ajouter à My VHL
Imprimer
XML
PubMed Links
Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Virus de la grippe A / Vaccins antigrippaux / Épitopes immunodominants / Anticorps neutralisants / Hémagglutinines / Épitopes Limites: Animals Langue: En Journal: Proc Natl Acad Sci U S A Année: 2019 Type de document: Article