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There are currently no FDA-approved vaccines for the prevention of arenavirus disease, and therapeutic treatment is limited to the use of ribavirin and\/or immune plasma for a subset of the pathogenic arenaviruses. The considerable genetic variability observed among the seven arenaviruses that are pathogenic for humans illustrates one of the major challenges for vaccine development today, namely, to overcome pathogen heterogeneity. Over the past 5 years, our group has tested several strategies to overcome pathogen heterogeneity, utilizing the pathogenic arenaviruses as a model system. Because T cells play a prominent role in protective immunity following arenavirus infection, we specifically focused on the development of human vaccines that would induce multivalent and cross-protective cell-mediated immune responses. To facilitate our vaccine development and testing, we conducted large-scale major histocompatibility complex (MHC) class I and class II epitope discovery on murine, nonhuman primate, and human backgrounds for each of the pathogenic arenaviruses, including the identification of protective HLA-restricted epitopes. Finally, using the murine model of lymphocytic choriomeningitis virus infection, we studied the phenotypic characteristics associated with immunodominant and protective T cell epitopes. This review summarizes the findings from our studies and discusses their application to future vaccine design.<\/jats:p><\/jats:sec>","DOI":"10.1128\/mmbr.00045-09","type":"journal-article","created":{"date-parts":[[2010,5,27]],"date-time":"2010-05-27T23:57:41Z","timestamp":1275004661000},"page":"157-170","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["Coverage of Related Pathogenic Species by Multivalent and Cross-Protective Vaccine Design: Arenaviruses as a Model System"],"prefix":"10.1128","volume":"74","author":[{"given":"Jason","family":"Botten","sequence":"first","affiliation":[{"name":"Department of Medicine, The University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, Vermont 05405-0068"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Sidney","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca R.","family":"Mothe\u0301","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, California State University, San Marcos, California 92096"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bjoern","family":"Peters","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Sette","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maya F.","family":"Kotturi","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(02)00786-3"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"4753","DOI":"10.4049\/jimmunol.159.10.4753","volume":"159","year":"1997","unstructured":"Alexander, J., C. 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