Abstract
Preventive vaccination is a highly promising strategy for interrupting leishmaniasis transmission that can, additionally, contribute to elimination. A vaccine formulation based on naturally excreted secreted (ES) antigens was prepared from L. infantum promastigote culture supernatant. This vaccine achieved successful results in Phase III trials and was licensed and marketed as CaniLeish. We recently showed that newly identified ES promastigote surface antigen (PSA), from both viable promastigotes and axenically-grown amastigotes, represented the major constituent and the highly immunogenic antigen of L. infantum and L. amazonensis ES products. We report here that three immunizations with either the recombinant ES LaPSA-38S (rPSA) or its carboxy terminal part LaPSA-12S (Cter-rPSA), combined with QA-21 as adjuvant, confer high levels of protection in naive L. infantum-infected Beagle dogs, as checked by bone marrow parasite absence in respectively 78.8% and 80% of vaccinated dogs at 6 months post-challenge. The parasite burden in infected vaccinated dogs was significantly reduced compared to placebo group, as measured by q-PCR. Moreover, our results reveal humoral and cellular immune response clear-cut differences between vaccinated and control dogs. An early increase in specific IgG2 antibodies was observed in rPSA/QA-21- and Cter-rPSA/QA-21-immunized dogs only. They were found functionally active in vitro and were highly correlated with vaccine protection. In vaccinated protected dogs, IFN-γ and NO productions, as well as anti-leishmanial macrophage activity, were increased. These data strongly suggest that ES PSA or its carboxy-terminal part, in recombinant forms, induce protection in a canine model of zoonotic visceral leishmaniasis by inducing a Th1-dominant immune response and an appropriate specific antibody response. These data suggest that they could be considered as important active components in vaccine candidates.
Highlights
Leishmaniasis is among the most severe parasitic infections affecting humans and dogs in the world
Visceral leishmaniasis (VL), a potentially fatal disease caused by L. infantum, represents perfectly the need for a “One Health” approach for disease control, since it affects both humans and dogs, with similar clinical outcome and T-cell mediated immunity commitment
The results indicate that recombinant forms of soluble promastigote surface antigen (PSA) are very promising effective vaccine candidates against canine visceral disease (VL)
Summary
Leishmaniasis is among the most severe parasitic infections affecting humans and dogs in the world. It is the second-highest number of deaths caused by parasites worldwide. Infection is provoked by protozoans of the genus Leishmania, transmitted by the bite of different species of phlebotomine sandflies. They replicate within host mononuclear phagocytes [2,3,4]. Leishmania parasites cause a wide spectrum of human diseases ranging from asymptomatic disease, self-healing cutaneous (CL), to disfiguring diffuse cutaneous leishmaniasis (DCL) or mutilating mucosal infections (MCL), and from subclinical to acute visceral disease (VL) that results in death in susceptible people, causing more than 59,000 deaths annually [1,5]
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