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

Centro Interdisciplinar de Terapia Gênica - Universidade Federal de São Paulo - Escola Paulista de Medicina, Rua Mirassol, 207, São Paulo, SP, 04044-010, Brazil; Disciplina de Parasitologia - Departamento de Microbiologia e Imunologia, Universidade Federal de São Paulo - Escola Paulista de Medicina, Rua Botucatu, 862, 6° andar, São Paulo, SP, 04023-062, Brazil, Disciplina de Imunologia - Departamento de Microbiologia Imunonologia e Parasitologia - Universidade Federal de Goiânia, Goiânia, Brazil; Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão, 121, Salvador, BA, 40295-001, Brazil; Departamento de Biointeração, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Av. Reitor Miguel Calmon, S/N, Salvador, BA, 40110-160, Brazil

^* To whom correspondence should be addressed. Email: mrodrigues{at}ecb.epm.br.

	Abstract

We evaluated whether four recombinant antigens previously used for vaccination against experimental infection with Leishmania (Leishmania) major could also induce protective immunity against a challenge with L. (Viannia) braziliensis, the species responsible for 90% of the 28,712 annual cases of cutaneous and muco-cutaneous leishmaniais recorded in Brazil during the year of 2004. Initially, we isolated the homolog genes encoding four L. (V.) braziliensis antigens: i) homologue of receptor for activated C kinase, ii) thiol-specific antioxidant, iii) Leishmania elongation and initiation factor and iv) Leishmania major stress-inducible protein 1. At the deduced amino acid level, all four open reading frames had a high degree of identity with the previously described genes of L. (L.) major being expressed on promastigotes and amastigotes of L. (V.) braziliensis. These genes were inserted into the vector pcDNA3 or expressed as bacterial recombinant proteins. After immunization with recombinant plasmids or proteins, BALB/c mice generated specific antibody or cell-mediated immune responses (Interferon- production). After an intra-dermal challenge with L. (V.) braziliensis infective promastigotes, no significant reduction on the lesions was detected. We conclude that the protective immunity afforded by these four vaccine candidates against experimental cutaneous leishmaniasis caused by L. (L.) major could not be reproduced against a challenge with L. (V.) braziliensis. Although negative, we consider our results important as they suggest that studies aimed at the development of an effective vaccine against L. (V.) braziliensis, the main causative agent of cutaneous leishmaniasis in the New World, should be redirected towards distinct antigens or different vaccination strategies.