Diverse recognition of conserved orthopoxvirus CD8+ T cell epitopes in vaccinated rhesus macaques

• Published in: Vaccine Vol. 27; no. 36; pp. 4990 - 5000
• Main Authors: Walsh, Stephen R, Gillis, Jacqueline, Peters, Björn, Mothé, Bianca R, Sidney, John, Sette, Alessandro, Johnson, R. Paul
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 06.08.2009; Elsevier; Elsevier Limited
• Subjects: Allergy and Immunology; Animals; Applied microbiology; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Epitopes, T-Lymphocyte - immunology; Fundamental and applied biological sciences. Psychology; Histocompatibility Antigens Class I - immunology; Humans; Infections; Interferon-gamma - metabolism; Laboratory animals; Macaca mulatta; Microbiology; Miscellaneous; Non-human primates; Orthopoxvirus; Peptides; Poxvirus; Primates; Smallpox; Smallpox Vaccine - immunology; T cell epitopes; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccinia virus; Vaccinia virus - immunology; Variola; Virology; United States > US; Vaccinia virus; T cell epitopes; Non-human primates; Chordopoxvirinae; Antigenic determinant; Orthopoxvirus; Monkey; Macaca mulatta; Vaccine; Virus; Vertebrata; Mammalia; Poxviridae; T-Lymphocyte; Primates; Simioidea; Recognition
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2009.05.077

Abstract Vaccinia virus (VACV) induces a vigorous virus-specific CD8+ T cell response that plays an important role in control of poxvirus infection. To identify immunodominant poxvirus proteins and to facilitate future testing of smallpox vaccines in non-human primates, we used an algorithm for the prediction of VACV peptides able to bind to the common macaque MHC class I molecule Mamu-A*01. We synthesized 294 peptides derived from 97 VACV ORFs; 100 of these peptides did not contain the canonical proline at position three of the Mamu-A*01 binding motif. Cellular immune responses in PBMC from two vaccinia-vaccinated Mamu-A*01 + macaques were assessed by IFNγ ELISPOT assays. Vaccinated macaques recognized 17 peptides from 16 different ORFs with 6 peptides recognized by both macaques. Comparison with other orthopoxvirus sequences revealed that 12 of these epitopes are strictly conserved between VACV, variola, and monkeypoxvirus. ELISPOT responses were also observed to eight epitopes that did not contain the canonical P3 proline. These results suggest that the virus-specific CD8+ T cell response is broadly directed against multiple VACV proteins and that a subset of these T cell epitopes is highly conserved among orthopoxviruses.