This Article Full Text Full Text (PDF) 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.

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

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.

Editor: B. B. Finlay

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]  
• Badiee, A., Jaafari, M. R., Samiei, A., Soroush, D., Khamesipour, A. (2008). Coencapsulation of CpG Oligodeoxynucleotides with Recombinant Leishmania major Stress-Inducible Protein 1 in Liposome Enhances Immune Response and Protection against Leishmaniasis in Immunized BALB/c Mice. CVI 15: 668-674 [Abstract] [Full Text]  
• Coler, R. N., Goto, Y., Bogatzki, L., Raman, V., Reed, S. G. (2007). Leish-111f, a Recombinant Polyprotein Vaccine That Protects against Visceral Leishmaniasis by Elicitation of CD4+ T Cells. Infect. Immun. 75: 4648-4654 [Abstract] [Full Text]  
• Salay, G., Dorta, M. L., Santos, N. M., Mortara, R. A., Brodskyn, C., Oliveira, C. I., Barbieri, C. L., Rodrigues, M. M. (2007). Testing of Four Leishmania Vaccine Candidates in a Mouse Model of Infection with Leishmania (Viannia) braziliensis, the Main Causative Agent of Cutaneous Leishmaniasis in the New World. CVI 14: 1173-1181 [Abstract] [Full Text]  
• Tonui, W. K., Mejia, J. S., Hochberg, L., Mbow, M. L., Ryan, J. R., Chan, A. S. T., Martin, S. K., Titus, R. G. (2004). Immunization with Leishmania major Exogenous Antigens Protects Susceptible BALB/c Mice against Challenge Infection with L. major. Infect. Immun. 72: 5654-5661 [Abstract] [Full Text]  
• VANLOUBBEECK, Y., JONES, D. E. (2004). The Immunology of Leishmania Infection and the Implications for Vaccine Development. Ann. N. Y. Acad. Sci. 1026: 267-272 [Abstract] [Full Text]  
• Campbell, K., Diao, H., Ji, J., Soong, L. (2003). DNA Immunization with the Gene Encoding P4 Nuclease of Leishmania amazonensis Protects Mice against Cutaneous Leishmaniasis. Infect. Immun. 71: 6270-6278 [Abstract] [Full Text]  
• Iborra, S., Soto, M., Carrion, J., Nieto, A., Fernandez, E., Alonso, C., Requena, J. M. (2003). The Leishmania infantum Acidic Ribosomal Protein P0 Administered as a DNA Vaccine Confers Protective Immunity to Leishmania major Infection in BALB/c Mice. Infect. Immun. 71: 6562-6572 [Abstract] [Full Text]