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Infection and Immunity, February 2005, p. 812-819, Vol. 73, No. 2
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.2.812-819.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Cross-Protective Efficacy of a Prophylactic Leishmania donovani DNA Vaccine against Visceral and Cutaneous Murine Leishmaniasis

Ingrid Aguilar-Be,1 Renata da Silva Zardo,2 Edilma Paraguai de Souza,2 Gulnara Patrícia Borja-Cabrera,2 Miguel Rosado-Vallado,1 Mirza Mut-Martin,3 Maria del Rosario García-Miss,3 Clarisa Beatriz Palatnik de Sousa,2 and Eric Dumonteil1*

Laboratorio de Parasitología,1 Laboratorio de Inmunobiología, Centro de Investigaciones Regionales "Dr. Hideyo Noguchi," Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico,3 Instituto de Microbiologia "Professor Paulo de Góes," Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil2

Received 27 July 2004/ Returned for modification 12 September 2004/ Accepted 8 October 2004

The fucose-mannose ligand (FML) complex of Leishmania donovani is a promising vaccine candidate against murine and canine visceral leishmaniasis, and its main component is a 36-kDa nucleoside hydrolase (NH36). In this study, we tested the immune response and protection induced by the purified FML, the recombinant NH36 (rNH36), and NH36 DNA vaccines against the agents of visceral (L. chagasi) and cutaneous (L. mexicana) leishmaniasis in BALB/c mice. Mice developed weak humoral response to the vaccines alone, except for those immunized with FML. However, all three vaccine groups presented elevated immunoglobulin G (IgG), IgG1, and IgG2a levels after infection with L. chagasi, whereas no differences were observed between vaccine and control groups after infection with L. mexicana. A strong intradermal reaction to L. donovani and L. mexicana antigens was observed in mice immunized with rNH36 or FML, whereas mice immunized with NH36 DNA only reacted against L. donovani antigens. Experimental infection of immunized mice demonstrated that FML and rNH36 induced significant protection against L. chagasi infection with reductions in parasite loads of 79%. FML also conferred partial protection against L. mexicana infection. The best protection was observed in mice immunized with the VR1012-NH36 DNA vaccine, which induced an 88% reduction in L. chagasi parasite load and a 65% reduction in L. mexicana lesion size. Fluorescence-activated cell sorting analysis indicated the DNA vaccine induced a two- to fivefold increase in gamma interferon-producing CD4+ T cells, indicating a Th1-type immune response. Our results showed that the NH36 DNA vaccine induced a strong immunoprotection against visceral and cutaneous leishmaniasis, suggesting that this DNA vaccine represents a very good candidate for use against several Leishmania species.

* Corresponding author. Mailing address: Laboratorio de Parasitología, Centro de Investigaciones Regionales "Dr. Hideyo Noguchi," Universidad Autónoma de Yucatán, Ave. Itzaes #490 x 59, 97000 Mérida, Yucatán, Mexico. Phone: (52) 999-924-5910. Fax: (52) 999-923-6120. E-mail: oliver{at}tunku.uady.mx.

Editor: W. A. Petri, Jr.

Infection and Immunity, February 2005, p. 812-819, Vol. 73, No. 2
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.2.812-819.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Samant, M., Gupta, R., Kumari, S., Misra, P., Khare, P., Kushawaha, P. K., Sahasrabuddhe, A. A., Dube, A. (2009). Immunization with the DNA-Encoding N-Terminal Domain of Proteophosphoglycan of Leishmania donovani Generates Th1-Type Immunoprotective Response against Experimental Visceral Leishmaniasis. J. Immunol. 183: 470-479 [Abstract] [Full Text]  
  • Al-Wabel, M. A., Tonui, W. K., Cui, L., Martin, S. K., Titus, R. G. (2007). Protection of Susceptible BALB/c Mice from Challenge with Leishmania major by Nucleoside Hydrolase, a Soluble Exo-antigen of Leishmania. Am J Trop Med Hyg 77: 1060-1065 [Abstract] [Full Text]  


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