This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.00394-07v1 75/9/4648    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Coler, R. N. Articles by Reed, S. G. Search for Related Content PubMed PubMed Citation Articles by Coler, R. N. Articles by Reed, S. G.

Leish-111f, a Recombinant Polyprotein Vaccine That Protects against Visceral Leishmaniasis by Elicitation of CD4⁺ T Cells

Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, Washington 98104

Received 15 March 2007/ Returned for modification 23 April 2007/ Accepted 20 June 2007

The Leishmania-derived recombinant polyprotein Leish-111f or its three component proteins, thiol-specific antioxidant (TSA), Leishmania major stress-inducible protein 1 (LmSTI1), and Leishmania elongation initiation factor (LeIF), have previously been demonstrated to be efficacious against cutaneous or mucosal leishmaniasis in mice, nonhuman primates, and humans. In this study we demonstrate that Leish-111f is also a vaccine antigen candidate against visceral leishmaniasis (VL) caused by Leishmania infantum. 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⁺ 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 L. infantum 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 Leishmania 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.

Published ahead of print on 2 July 2007.

Editor: W. A. Petri, Jr.

This article has been cited by other articles:

• Dey, A., Sharma, P., Redhu, N. S., Singh, S. (2008). Kinesin Motor Domain of Leishmania donovani as a Future Vaccine Candidate. CVI 15: 836-842 [Abstract] [Full Text]