Protective immunity provided by HLA-A2 epitopes for fusion and hemagglutinin proteins of measles virus

• Published in: Virology (New York, N.Y.) N.Y.), 2006-09, Vol.352 (2), p.390-399
• Main Authors: Oh, SangKon, Stegman, Brian, Pendleton, C. David, Ota, Martin O., Pan, Chien-Hsiung, Griffin, Diane E., Burke, Donald S., Berzofsky, Jay A.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antigen Presentation; Antigens, Viral - genetics; Antigens, Viral - metabolism; Binding Sites - genetics; CD8; CD8-Positive T-Lymphocytes - immunology; Cytotoxic T lymphocytes; Epitopes; Epitopes - genetics; Epitopes - immunology; Hemagglutinins, Viral - immunology; Hemagglutinins, Viral - physiology; HLA-A2 Antigen - genetics; HLA-A2 Antigen - immunology; Humans; Measles; Measles Vaccine - genetics; Measles Vaccine - immunology; Measles virus; Measles virus - immunology; Measles virus - pathogenicity; Measles virus - physiology; Mice; Mice, Transgenic; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Vaccines; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Vaccinia virus - genetics; Vaccinia virus - immunology; Viral Fusion Proteins - immunology; Viral Fusion Proteins - physiology
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2006.04.040

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.