title: Protective immunity provided by HLA-A2 epitopes for fusion and hemagglutinin proteins of measles virus.
abstract: Natural infection and vaccination with a live-attenuated measles virus (MV) induce CD8(+) T-cell-mediated immune responses that may play a central role in controlling MV infection. In this study, we show that newly identified human HLA-A2 epitopes from MV hemagglutinin (H) and fusion (F) proteins induced protective immunity in HLA-A2 transgenic mice challenged with recombinant vaccinia viruses expressing F or H protein. HLA-A2 epitopes were predicted and synthesized. Five and four peptides from H and F, respectively, bound to HLA-A2 molecules in a T2-binding assay, and four from H and two from F could induce peptide-specific CD8+ T cell responses in HLA-A2 transgenic mice. Further experiments proved that three peptides from H (H9-567, H10-250, and H10-516) and one from F protein (F9-57) were endogenously processed and presented on HLA-A2 molecules. All peptides tested in this study are common to 5 different strains of MV including Edmonston. In both A2K(b) and HHD-2 mice, the identified peptide epitopes induced protective immunity against recombinant vaccinia viruses expressing H or F. Because F and H proteins induce neutralizing antibodies, they are major components of new vaccine strategies, and therefore data from this study will contribute to the development of new vaccines against MV infection.
authors.affiliation: Vaccine Branch, National Cancer Institute, National Institutes of Health, Bldg. 10-Rm 6B-09, NIH, Bethesda, MD 20892-1578, USA. sangkono@baylorhealth.edu
authors.forename: SangKon
authors.initials: S
authors.lastname: Oh
authors.forename: Brian
authors.initials: B
authors.lastname: Stegman
authors.forename: C David
authors.initials: CD
authors.lastname: Pendleton
authors.forename: Martin O
authors.initials: MO
authors.lastname: Ota
authors.forename: Chien-Hsiung
authors.initials: CH
authors.lastname: Pan
authors.forename: Diane E
authors.initials: DE
authors.lastname: Griffin
authors.forename: Donald S
authors.initials: DS
authors.lastname: Burke
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006389:Hemagglutinins, Viral / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008458:Measles Vaccine / Q000235:genetics / Q000276:immunology; D008459:Measles virus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014760:Viral Fusion Proteins / Q000276:immunology* / Q000502:physiology
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D015789:HLA-A2 Antigen; D006389:Hemagglutinins, Viral; D008458:Measles Vaccine; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014760:Viral Fusion Proteins; C032397:hemagglutinin protein G, measles virus