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Immune Responses Induced by the Leishmania (Leishmania) donovani A2 Antigen, but Not by the LACK Antigen, Are Protective against Experimental Leishmania (Leishmania) amazonensis Infection

Eduardo Antonio Ferraz Coelho,¹ Carlos Alberto Pereira Tavares,¹ Fernando Aécio Amorim Carvalho,^1, Karina Figueiredo Chaves,² Kadima Nayara Teixeira,¹ Rafaela Chitarra Rodrigues,¹ Hugues Charest,³ Greg Matlashewski,⁴ Ricardo Tostes Gazzinelli,^1,5 and Ana Paula Fernandes^2*

Department of Biochemistry and Immunology,¹ School of Pharmacy, Universidade Federal de Minas Gerais,² Universidade Federal de Minas Gerais, and Laboratory of Immunopathology, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz,⁵ Laboratory of Immunopathology, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil,⁴ Department of Microbiology and Immunology, McGill University, Montreal, and Laboratoire de Santé Publique du Québec, Québec, Canada³

Received 2 December 2002/ Returned for modification 23 January 2003/ Accepted 14 April 2003

Leishmania amazonensis is one of the major etiologic agents of a broad spectrum of clinical forms of leishmaniasis and has a wide geographical distribution in the Americas, which overlaps with the areas of transmission of many other Leishmania species. The LACK and A2 antigens are shared by various Leishmania species. A2 was previously shown to induce a potent Th1 immune response and protection against L. donovani infection in BALB/c mice. LACK is effective against L. major infection, but no significant protection against L. donovani infection was observed, in spite of the induction of a potent Th1 immune response. In an attempt to select candidate antigens for an American leishmaniasis vaccine, we investigated the protective effect of these recombinant antigens (rLACK and rA2) and recombinant interleukin-12 (rIL-12) against L. amazonensis infection in BALB/c mice. As expected, immunization with either rA2-rIL-12 or rLACK-rIL-12 induced a robust Th1 response prior to infection. However, only the BALB/c mice immunized with rA2-rIL-12 were protected against infection. Sustained gamma interferon (IFN-) production, high levels of anti-A2 antibodies, and low levels of parasite-specific antibodies were detected in these mice after infection. In contrast, mice immunized with rLACK-rIL-12 displayed decreased levels of IFN- and high levels of both anti-LACK and parasite-specific antibodies. Curiously, the association between rA2 and rLACK antigens in the same vaccine completely inhibited the rA2-specific IFN- and humoral responses and, consequently, the protective effect of the rA2 antigen against L. amazonensis infection. We concluded that A2, but not LACK, fits the requirements for a safe vaccine against American leishmaniasis.

Editor: J. M. Mansfield

Present address: Department of Biochemistry and Pharmacology, Universidade Federal do Piauí, Terezina, Piauí, 64049-550, Brazil.

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