Long-term T cell memory to human leucocyte antigen-A2 supertype epitopes in humans vaccinated against smallpox
Department of Quantitative Health Sciences; Department of Pediatrics
Adult; Aged; Algorithms; Amino Acid Sequence; Computational Biology; Enzyme-Linked Immunosorbent Assay; Epitopes, T-Lymphocyte; HLA-A2 Antigen; Histocompatibility Testing; Humans; Immunologic Memory; Interferon-gamma; Middle Aged; Peptide Fragments; Smallpox; Smallpox Vaccine; T-Lymphocyte Subsets; Vaccinia virus
Biostatistics | Epidemiology | Health Services Research | Immunology and Infectious Disease
Identification of human leucocyte antigen (HLA) class I-restricted T cell epitopes is important to develop methods to track the evolution of T cell memory to new generation smallpox vaccines and allow comparison to older vaccinia virus preparations known to induce protection against smallpox. We evaluated the relative predictive values of four computational algorithms to identify candidate 9-mer HLA-A2 supertype epitopes that were confirmed to stimulate preferentially T cell interferon (IFN)-gamma responses by subjects last vaccinated with Dryvax 27-54 years previously. Six peptides encoded by I4L, G1L, A8R, I8R, D12L and H3L open reading frames that were identical for Vaccinia (Copenhagen), Variola major (Bangledesh 1975) and modified vaccinia Ankara strain preferentially stimulated IFN-gamma responses by healthy HLA-A2 supertype adults last given Dryvax 27-49 years earlier relative to remotely vaccinated non-HLA-A2 supertype and unvaccinated HLA-A2 supertype adults. Combining results from at least two computational algorithms that use different strategies to predict peptide binding to HLA-A2 supertype molecules was optimal for selection of candidate peptides that were confirmed to be epitopes by recall of T cell IFN-gamma responses. These data will facilitate evaluation of the immunogenicity of replication incompetent smallpox vaccines such as modified vaccinia Ankara and contribute to knowledge of poxvirus epitopes that are associated with long-lived T cell memory.
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Citation: Clin Exp Immunol. 2007 Aug;149(2):265-73. Epub 2007 May 4. Link to article on publisher's site
Clinical and experimental immunology
Ostrout, N. D.; McHugh, Marilyn M.; Tisch, Daniel J.; Moormann, Ann M.; Brusic, V.; and Kazura, James W., "Long-term T cell memory to human leucocyte antigen-A2 supertype epitopes in humans vaccinated against smallpox" (2007). Quantitative Health Sciences Publications and Presentations. 398.