title: 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.
authors.affiliation: IRD, UMR 177 INTERTRYP IRD CIRAD, Montpellier, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Petitdidier
authors.affiliation: IRD, UMR 177 INTERTRYP IRD CIRAD, Montpellier, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Pagniez
authors.affiliation: Virbac Animal Health, Carros, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Papierok
authors.affiliation: University Hospital of Bordeaux, Laboratoire de Parasitologie-Mycologie, Bordeaux, France.|Université de Bordeaux, UMR 177 INTERTRYP IRD CIRAD, Bordeaux, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Vincendeau
authors.affiliation: IRD, UMR 177 INTERTRYP IRD CIRAD, Montpellier, France.
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Lemesre
authors.affiliation: IRD, UMR 177 INTERTRYP IRD CIRAD, Montpellier, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Bras-Gonçalves
mesh_terms: D056704:Adaptive Immunity; D000276:Adjuvants, Immunologic; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D001853:Bone Marrow / Q000469:parasitology; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D004285:Dogs; D005260:Female; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D018314:Leishmania infantum / Q000276:immunology* / Q000502:physiology; D007894:Leishmania mexicana / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control* / Q000662:veterinary; D008264:Macrophages / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D059208:Parasite Load; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D007074:Immunoglobulin G; D054332:Leishmaniasis Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C110913:surface antigen protein, Leishmania; D009569:Nitric Oxide; D007371:Interferon-gamma