Recombinant Forms of Leishmania amazonensis Excreted/Secreted Promastigote Surface Antigen (PSA) Induce Protective Immune Responses in Dogs

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.

Trypanosomatid Infections: How Do Parasites and Their Excreted–Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages?

“…Interestingly, ES from L. infantum elicited a protective immune response in dogs, their natural hosts, by triggering a Th1-dominant immune response and an appropriate specific antibody response, thereby countering the parasite-induced arginase metabolism early on, and leading to the first anti-Leishmania vaccine commercially available in Europe ( 159 – 161 ). More recently, a secreted promastigote surface antigen, one of the main constituents and the highly immunogenic antigen of Leishmania , was shown to confer high levels of protection in naive dogs ( 162 ).…”

Leishmania Immunity: Advancing Immunotherapy and Vaccine Development

“…The authors showed that LetiFend ® can prevent the development of leishmaniasis in six-month-old dogs after natural infection with Leishmania infantum [101]. Recently, it was shown that the administration of recombinant ES LaPSA-38S (rPSA) or its carboxy terminal part (LaPSA-12S, Cter-rPSA), combined with QA-21 as adjuvant, conferred high levels of protection against L. infantum in beagles, as evidenced by a significant decrease in parasite burden and an increase in the Th1 immune response [102] Cross protection has been reported in vaccine studies in canine leishmaniasis. Roatt et al observed that the administration of a vaccine comprising of L. braziliensis antigens with saponin as an adjuvant (LBSap vaccine) conferred protection to dogs challenged with L. infantum mixed with salivary gland extracts.…”

Leishmaniasis in humans: drug or vaccine therapy?

“…In addition, administration of major immunogenic proteins provides path to generate integrated immune responses, especially against specified protective antigens. 124 …”