Outflanking immunodominance to target subdominant broadly neutralizing epitopes.

Autor:	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.; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, 40530 Gothenburg, Sweden., Kosik I; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892., Santos JJS; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892., Yewdell WT; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Boudreau CM; Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139.; PhD Program in Virology, Division of Medical Sciences, Harvard University, Boston, MA 02115., Mallajosyula VVA; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305., Mankowski MC; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892., Chambers M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892., Prabhakaran M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892., Hickman HD; Laboratory of Clinical Immunology and Microbiology, 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; Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139., Chaudhuri J; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Yewdell JW; 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.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Jul 02; Vol. 116 (27), pp. 13474-13479. Date of Electronic Publication: 2019 Jun 18.
DOI:	10.1073/pnas.1816300116
Abstrakt:	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. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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