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Cellular immunity, chiefly the CD8<jats:sup>+<\/jats:sup>T-cell response, plays a critical role in providing protective immunity following infection with the Old World arenaviruses LASV and LCMV. In the current study, we evaluated whether HLA class I-restricted epitopes that are cross-reactive among pathogenic arenaviruses could be identified for the purpose of developing an epitope-based vaccination approach that would cross-protect against multiple arenaviruses. We were able to identify a panel of HLA-A*0201-restricted peptides derived from the same region of the glycoprotein precursor (GPC) of LASV (GPC spanning residues 441 to 449 [GPC<jats:sub>441-449<\/jats:sub>]), LCMV (GPC<jats:sub>447-455<\/jats:sub>), JUNV (GPC<jats:sub>429-437<\/jats:sub>), MACV (GPC<jats:sub>444-452<\/jats:sub>), GTOV (GPC<jats:sub>427-435<\/jats:sub>), and WWAV (GPC<jats:sub>428-436<\/jats:sub>) that displayed high-affinity binding to HLA-A*0201 and were recognized by CD8<jats:sup>+<\/jats:sup>T cells in a cross-reactive manner following LCMV infection or peptide immunization of HLA-A*0201 transgenic mice. Immunization of HLA-A*0201 mice with the Old World peptide LASV GPC<jats:sub>441-449<\/jats:sub>or LCMV GPC<jats:sub>447-455<\/jats:sub>induced high-avidity CD8<jats:sup>+<\/jats:sup>T-cell responses that were able to kill syngeneic target cells pulsed with either LASV GPC<jats:sub>441-449<\/jats:sub>or LCMV GPC<jats:sub>447-455<\/jats:sub><jats:italic>in vivo<\/jats:italic>and provided significant protection against viral challenge with LCMV. Through this study, we have demonstrated that HLA class I-restricted, cross-reactive epitopes exist among diverse arenaviruses and that individual epitopes can be utilized as effective vaccine determinants for multiple pathogenic arenaviruses.<\/jats:p>","DOI":"10.1128\/jvi.00672-10","type":"journal-article","created":{"date-parts":[[2010,7,29]],"date-time":"2010-07-29T08:37:55Z","timestamp":1280392675000},"page":"9947-9956","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["A Multivalent Vaccination Strategy for the Prevention of Old World Arenavirus Infection in Humans"],"prefix":"10.1128","volume":"84","author":[{"given":"Jason","family":"Botten","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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