Abstract
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.
Highlights
Leishmania infections are vector-borne neglected diseases caused by Leishmania spp. protozoan parasites transmitted by phlebotomine sand flies
Canine visceral leishmaniasis (CVL) is a severe disease characterized by chronic evolution of viscerocutaneous signs, which is of great importance in Europe for both public health and in veterinary medicine
Using Leishmania excreted/secreted products, we previously showed that soluble promastigote surface antigens (PSA) were characterized as immunodominant excreted/secreted components of Leishmania amazonensis and L. infantum.[22]
Summary
Leishmania infections are vector-borne neglected diseases caused by Leishmania spp. protozoan parasites transmitted by phlebotomine sand flies. They are responsible for the secondhighest number of deaths due to parasitic infections worldwide, and are overwhelmingly associated with poverty.[1,2]. At least 2.5 million dogs are probably infected and severely affected dogs do not survive.[5] Both symptomatically and asymptomatically infected dogs can be considered as a reservoir of the parasite involved in the transmission cycle of L. infantum in dogs and humans.[6] In ZVL-endemic regions of the Mediterranean and Latin America, a high prevalence of canine infection is associated with a high risk of human disease.[7]
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