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In this study we demonstrate that Leish-111f is also a vaccine antigen candidate against visceral leishmaniasis (VL) caused by<jats:italic>Leishmania infantum<\/jats:italic>. We evaluated the immune response and protection induced by Leish-111f formulated with monophosphoryl lipid A in a stable emulsion (Leish-111f+MPL-SE) and demonstrated that mice developed strong humoral and T-cell responses to the vaccine antigen. Analysis of the cellular immune responses of immunized, uninfected mice demonstrated that the vaccine induced a significant increase in CD4<jats:sup>+<\/jats:sup>T cells producing gamma interferon, interleukin 2, and tumor necrosis factor cytokines, indicating a Th1-type immune response. Experimental infection of immunized mice and hamsters demonstrated that Leish-111f+MPL-SE induced significant protection against<jats:italic>L. infantum<\/jats:italic>infection, with reductions in parasite loads of 99.6%, a level of protection greater than that reported for other vaccine candidates in animal models of VL. Taken together, our results suggest that this vaccine represents a good candidate for use against several<jats:italic>Leishmania<\/jats:italic>species. The Leish-111f+MPL-SE product we report here is the first defined vaccine for leishmaniasis in human clinical trials and has completed phase 1 and 2 safety and immunogenicity testing in normal, healthy human subjects.<\/jats:p>","DOI":"10.1128\/iai.00394-07","type":"journal-article","created":{"date-parts":[[2007,7,3]],"date-time":"2007-07-03T00:34:01Z","timestamp":1183422841000},"page":"4648-4654","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":175,"title":["Leish-111f, a Recombinant Polyprotein Vaccine That Protects against Visceral Leishmaniasis by Elicitation of CD4<sup>+<\/sup>T Cells"],"prefix":"10.1128","volume":"75","author":[{"given":"Rhea N.","family":"Coler","sequence":"first","affiliation":[{"name":"Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, Washington 98104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Goto","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, Washington 98104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Bogatzki","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, Washington 98104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanitha","family":"Raman","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, Washington 98104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"Reed","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, Washington 98104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.11.7160"},{"key":"e_1_3_2_3_2","first-page":"137","volume":"30","year":"2000","unstructured":"Bebars, M. 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