Protective immunity provided by HLA-A2 epitopes for fusion and hemagglutinin proteins of measles virus.
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.
Oh
SangKon
S
Vaccine Branch, National Cancer Institute, National Institutes of Health, Bldg. 10-Rm 6B-09, NIH, Bethesda, MD 20892-1578, USA. sangkono@baylorhealth.edu
Stegman
Brian
B
Pendleton
C David
CD
Ota
Martin O
MO
Pan
Chien-Hsiung
CH
Griffin
Diane E
DE
Burke
Donald S
DS
Berzofsky
Jay A
JA
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
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