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Infection and Immunity, August 2002, p. 4215-4225, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4215-4225.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Immunization with a Polyprotein Vaccine Consisting of the T-Cell Antigens Thiol-Specific Antioxidant, Leishmania major Stress-Inducible Protein 1, and Leishmania Elongation Initiation Factor Protects against Leishmaniasis

Rhea N. Coler,1* Yasir A. W. Skeiky,2 Karen Bernards,1 Kay Greeson,1 Darrick Carter,2 Charisa D. Cornellison,2 Farrokh Modabber,1 Antonio Campos-Neto,1 and Steven G. Reed1,2

Infectious Disease Research Institute,1 Corixa Corporation, Seattle, Washington 981042

Received 13 February 2002/ Returned for modification 2 May 2002/ Accepted 13 May 2002

Development of an effective vaccine against Leishmania infection is a priority of tropical disease research. We have recently demonstrated protection against Leishmania major in the murine and nonhuman primate models with individual or combinations of purified leishmanial recombinant antigens delivered as plasmid DNA constructs or formulated with recombinant interleukin-12 (IL-12) as adjuvant. In the present study, we immunized BALB/c mice with a recombinant polyprotein comprising a tandem fusion of the leishmanial antigens thiol-specific antioxidant, L. major stress-inducible protein 1 (LmSTI1), and Leishmania elongation initiation factor (LeIF) delivered with adjuvants suitable for human use. Aspects of the safety, immunogenicity, and vaccine efficacy of formulations with each individual component, as well as the polyprotein referred to as Leish-111f, were assessed by using the L. major challenge model with BALB/c mice. No adverse reactions were observed when three subcutaneous injections of the Leish-111f polyprotein formulated with either MPL-squalene (SE) or Ribi 529-SE were given to BALB/c mice. A predominant Th1 immune response characterized by in vitro lymphocyte proliferation, gamma interferon production, and immunoglobulin G2A antibodies was observed with little, if any, IL-4. Moreover, Leish-111f formulated with MPL-SE conferred immunity to leishmaniasis for at least 3 months. These data demonstrate success at designing and developing a prophylactic leishmaniasis vaccine that proved effective in a preclinical model using multiple leishmanial antigens produced as a single protein delivered with a powerful Th1 adjuvant suitable for human use.

* Corresponding author. Mailing address: Infectious Disease Research Institute, 1124 Columbia St., Suite 600, Seattle, WA 98104. Phone: (206) 381-0883. Fax: (206) 381-3678. E-mail: coler{at}idri.org.

Editor: B. B. Finlay

Infection and Immunity, August 2002, p. 4215-4225, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4215-4225.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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