title: Identification and characterization of new Leishmania promastigote surface antigens, LaPSA-38S and LiPSA-50S, as major immunodominant excreted/secreted components of L. amazonensis and L. infantum.
abstract: We have previously demonstrated that sera from dogs vaccinated with excreted/secreted antigens (ESA) of Leishmania infantum promastigotes (LiESAp) mainly recognized an immunodominant antigen of 54 kDa. An anti-LiESAp-specific IgG2 humoral response was observed and associated to Th1-type response in vaccinated dogs. This response was highly correlated with a long-lasting and strong LiESAp-vaccine protection toward L. infantum experimental infection. In addition, it was also shown that dogs from the vaccinated group developed a selective IgG2 response against an immunodominant antigen of 45 kDa of Leishmania amazonensis ESA promastigotes (LaESAp). In order to identify and characterize these immunodominant antigens, a mouse monoclonal antibody (mAb F5) was produced by immunization against LaESAp. It was found to recognize the major antigenic targets of both LaESAp and LiESAp. Analysis with mAb F5 of L. amazonensis amastigote and promastigote cDNA expression libraries enabled the identification of clones encoding proteins with significant structural homology to the promastigote surface antigens named PSA-2/gp-46. Among them, one clone presented a full-length cDNA and encoded a novel L. amazonensis protein of 38.6 kDa calculated molecular mass (LaPSA-38S) sharing an amino acid sequence consistent with that of the PSA polymorphic family and a N-terminal signal peptide, characteristic of a secreted protein. We then screened a L. infantum promastigote DNA cosmid library using a cDNA probe derived from the LaPSA-38S gene and identified a full-length clone of a novel excreted/secreted protein of L. infantum with a calculated molecular mass of 49.2 kDa and named LiPSA-50S. The fact that a significant immunological reactivity was observed against PSA, suggests that these newly identified proteins could have an important immunoregulatory influence on the immune response. This hypothesis is supported by the fact that (i) these proteins were naturally excreted/secreted by viable Leishmania promastigotes and amastigotes, and (ii) they are selectively recognized by vaccinated and protected dogs.
authors.affiliation: Institut de Recherche pour le Développement, UMR177 IRD/CIRAD "Interactions Hôtes-Vecteurs-Parasites dans les maladies infectieuses à trypanosomatidae", 911 avenue Agropolis, BP 64501, 34394 Montpellier cedex 5, France. Electronic address: rachel.bras@ird.fr.
authors.forename: Rachel
authors.initials: R
authors.lastname: Bras-Gonçalves
authors.affiliation: Institut de Recherche pour le Développement, UMR177 IRD/CIRAD "Interactions Hôtes-Vecteurs-Parasites dans les maladies infectieuses à trypanosomatidae", 911 avenue Agropolis, BP 64501, 34394 Montpellier cedex 5, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Petitdidier
authors.affiliation: Institut de Recherche pour le Développement, UMR177 IRD/CIRAD "Interactions Hôtes-Vecteurs-Parasites dans les maladies infectieuses à trypanosomatidae", 911 avenue Agropolis, BP 64501, 34394 Montpellier cedex 5, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Pagniez
authors.affiliation: Institut de Recherche pour le Développement, UMR177 IRD/CIRAD "Interactions Hôtes-Vecteurs-Parasites dans les maladies infectieuses à trypanosomatidae", 911 avenue Agropolis, BP 64501, 34394 Montpellier cedex 5, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Veyrier
authors.affiliation: Institut de Recherche pour le Développement, UMR177 IRD/CIRAD "Interactions Hôtes-Vecteurs-Parasites dans les maladies infectieuses à trypanosomatidae", 911 avenue Agropolis, BP 64501, 34394 Montpellier cedex 5, France.
authors.forename: Prisca
authors.initials: P
authors.lastname: Cibrelus
authors.affiliation: Institut de Recherche pour le Développement, UMR177 IRD/CIRAD "Interactions Hôtes-Vecteurs-Parasites dans les maladies infectieuses à trypanosomatidae", 911 avenue Agropolis, BP 64501, 34394 Montpellier cedex 5, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Cavaleyra
authors.affiliation: Institut de Recherche pour le Développement, UMR177 IRD/CIRAD "Interactions Hôtes-Vecteurs-Parasites dans les maladies infectieuses à trypanosomatidae", 911 avenue Agropolis, BP 64501, 34394 Montpellier cedex 5, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Maquaire
authors.affiliation: Institut de Recherche pour le Développement, UMR177 IRD/CIRAD "Interactions Hôtes-Vecteurs-Parasites dans les maladies infectieuses à trypanosomatidae", 911 avenue Agropolis, BP 64501, 34394 Montpellier cedex 5, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Moreaux
authors.affiliation: Institut de Recherche pour le Développement, UMR177 IRD/CIRAD "Interactions Hôtes-Vecteurs-Parasites dans les maladies infectieuses à trypanosomatidae", 911 avenue Agropolis, BP 64501, 34394 Montpellier cedex 5, France.
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Lemesre
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D001483:Base Sequence; D004283:Dog Diseases / Q000276:immunology / Q000469:parasitology*; D004285:Dogs / Q000097:blood / Q000469:parasitology*; D016056:Immunodominant Epitopes / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D018314:Leishmania infantum / Q000276:immunology*; D007894:Leishmania mexicana / Q000276:immunology*; D054332:Leishmaniasis Vaccines; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000517:prevention & control; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000276:immunology* / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014611:Vaccination
chemical_list: D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D054332:Leishmaniasis Vaccines; D015800:Protozoan Proteins; C110913:surface antigen protein, Leishmania
keywords: Excreted/secreted protein; Immunodominant; Leishmania; Vaccine candidate