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

•CDM/LP medium leads to purify naturally excreted/secreted Leishmania antigens (ESA).•Animals immunized with ESA lead to identify a major antigen of 45kDa in LaESAp.•Sera of LiESAp vaccinated dogs reveal a major antigen of 54kDa in LiESAp.•mAb F5 leads to identify LaPSA-38S and LiPSA-54S highly simi...

Full description

Saved in:
Bibliographic Details
Published in:Infection, genetics and evolution genetics and evolution, 2014-06, Vol.24, p.1-14
Main Authors: Bras-Gonçalves, Rachel, Petitdidier, Elodie, Pagniez, Julie, Veyrier, Renaud, Cibrelus, Prisca, Cavaleyra, Mireille, Maquaire, Sarah, Moreaux, Jérôme, Lemesre, Jean-Loup
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antibodies, Monoclonal - immunology
Antibodies, Protozoan - blood
Antibodies, Protozoan - immunology
Antigens, Protozoan - immunology
Antigens, Surface - immunology
Base Sequence
Dog Diseases - immunology
Dog Diseases - parasitology
Dogs - blood
Dogs - parasitology
Excreted/secreted protein
Immunodominant
Immunodominant Epitopes - immunology
Immunoglobulin G - immunology
Leishmania
Leishmania infantum - immunology
Leishmania mexicana - immunology
Leishmaniasis Vaccines
Leishmaniasis, Cutaneous - immunology
Leishmaniasis, Cutaneous - prevention & control
Leishmaniasis, Visceral - immunology
Leishmaniasis, Visceral - prevention & control
Molecular Sequence Data
Protozoan Proteins - immunology
Protozoan Proteins - secretion
Sequence Alignment
Sequence Analysis, DNA
Vaccination
Vaccine candidate
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•CDM/LP medium leads to purify naturally excreted/secreted Leishmania antigens (ESA).•Animals immunized with ESA lead to identify a major antigen of 45kDa in LaESAp.•Sera of LiESAp vaccinated dogs reveal a major antigen of 54kDa in LiESAp.•mAb F5 leads to identify LaPSA-38S and LiPSA-54S highly similar to PSA protein family.•mAb F5 leads to locate PSA proteins at Leishmania surface and in the flagellar pocket. 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 54kDa. 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 45kDa 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 38.6kDa 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 49.2kDa 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 vacci
ISSN:1567-1348
1567-7257
DOI:10.1016/j.meegid.2014.02.017