Résumé
Dogs are the main reservoir of zoonotic visceral leishmaniasis. Vaccination is a promising approach to help control leishmaniasis and to interrupt transmission of the Leishmania parasite. The promastigote surface antigen (PSA) is a highly immunogenic component of Leishmania excretory/secretory products. A vaccine based on three peptides derived from the carboxy-terminal part of Leishmania amazonensis PSA and conserved among Leishmania species, formulated with QA-21 as adjuvant, was tested on naive Beagle dogs in a preclinical trial. Four months after the full course of vaccination, dogs were experimentally infected with Leishmania infantum promastigotes. Immunization of dogs with peptide-based vaccine conferred immunity against experimental infection with L. infantum. Evidence for macrophage nitric oxide production and anti-leishmanial activity associated with IFN-γ production by lymphocytes was only found in the vaccinated group. An increase in specific IgG2 antibodies was also measured in vaccinated dogs from 2 months after immunization. Additionally, after challenge with L. infantum, the parasite burden was significantly lower in vaccinated dogs than in the control group. These data strongly suggest that this peptide-based vaccine candidate generated cross-protection against zoonotic leishmaniasis by inducing a Th1-type immune response associated with production of specific IgG2 antibodies. This preclinical trial including a peptide-based vaccine against leishmaniasis clearly demonstrates effective protection in a natural host. This approach deserves further investigation to enhance the immunogenicity of the peptides and to consider the possible engineering of a vaccine targeting several Leishmania species. Leishmaniasis, caused by the protozoan parasite Leishmania, can present in different forms depending on the infecting species. Visceral leishmaniasis is associated with migration of the parasite, in this case Leishmania infantum, to various organs and can infect both humans and canids. Here Rachel Bras-Gonçalves and colleagues test a Leishmania vaccine for dogs as they are the main reservoir for this zoonotic disease. The vaccine is based on the abundant immunogenic component of Leishmania excretory/secretory product, promastigote surface antigen (PSA); specifically, three peptides from the carboxyl-terminal of PSA, which is conserved in Leishmania species. Uninfected Beagle dogs were immunized with QA-21 as an adjuvant, and no local or systemic adverse reactions were observed. Four months later after three doses of the vaccine, dogs were infected with L. infantum promastigotes. Vaccination provided immunity with reduced parasite burden and this was associated with macrophage anti-leishmanial activity, increased IFN-y and nitric oxide production and increased Leishmania-specific IgG2 antibodies.