In vitro evaluation of a soluble Leishmania promastigote surface antigen as a potential vaccine candidate against human leishmaniasis.
PSA (Promastigote Surface Antigen) belongs to a family of membrane-bound and secreted proteins present in several Leishmania (L.) species. PSA is recognized by human Th1 cells and provides a high degree of protection in vaccinated mice. We evaluated humoral and cellular immune responses induced by a L. amazonensis PSA protein (LaPSA-38S) produced in a L. tarentolae expression system. This was done in individuals cured of cutaneous leishmaniasis due to L. major (CCLm) or L. braziliensis (CCLb) or visceral leishmaniasis due to L. donovani (CVLd) and in healthy individuals. Healthy individuals were subdivided into immune (HHR-Lm and HHR-Li: Healthy High Responders living in an endemic area for L. major or L. infantum infection) or non immune/naive individuals (HLR: Healthy Low Responders), depending on whether they produce high or low levels of IFN-γ in response to Leishmania soluble antigen. Low levels of total IgG antibodies to LaPSA-38S were detected in sera from the studied groups. Interestingly, LaPSA-38S induced specific and significant levels of IFN-γ, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-α in more. No significant cytokine response was observed in individuals immune to L. braziliensis or L. donovani infection. Phenotypic analysis showed a significant increase in CD4+ T cells producing IFN-γ after LaPSA-38S stimulation, in CCLm. A high positive correlation was observed between the percentage of IFN-γ-producing CD4+ T cells and the released IFN-γ. We showed that the LaPSA-38S protein was able to induce a mixed Th1 and Th2/Treg cytokine response in individuals with immunity to L. major or L. infantum infection indicating that it may be exploited as a vaccine candidate. We also showed, to our knowledge for the first time, the capacity of Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infection.
Laboratory of Medical Parasitology, Biotechnology and Biomolecules, LR11-IPT-06, Institut Pasteur de Tunis, Tunis, Tunisia.
Rym
R
Chamakh-Ayari
Institut de Recherche pour le Développement, UMR177 IRD/CIRAD «INTERTRYP», Montpellier, France.
Rachel
R
Bras-Gonçalves
Laboratory of Transmission, Control and Immunobiology of Infection, LR11-IPT-02, Institut Pasteur de Tunis, Tunis, Tunisie; UPSP EGEAL Institut Polytechnique LaSalle Beauvais, Beauvais, France.
Narges
N
Bahi-Jaber
Institut de Recherche pour le Développement, UMR177 IRD/CIRAD «INTERTRYP», Montpellier, France.
Elodie
E
Petitdidier
Laboratory of Medical Parasitology, Biotechnology and Biomolecules, LR11-IPT-06, Institut Pasteur de Tunis, Tunis, Tunisia.
Wafa
W
Markikou-Ouni
Laboratory of Medical Parasitology, Biotechnology and Biomolecules, LR11-IPT-06, Institut Pasteur de Tunis, Tunis, Tunisia.
Karim
K
Aoun
WHO Collaborating Center for Leishmaniasis, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Madrid, Spain.
Javier
J
Moreno
WHO Collaborating Center for Leishmaniasis, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Madrid, Spain.
Eugenia
E
Carrillo
National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.
Poonam
P
Salotra
National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.
Himanshu
H
Kaushal
National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.
Narender Singh
NS
Negi
Instituto de Medicina Tropical "Alexander von Humboldt", Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru.
Jorge
J
Arevalo
Instituto de Medicina Tropical "Alexander von Humboldt", Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru.
Francesca
F
Falconi-Agapito
Instituto de Medicina Tropical "Alexander von Humboldt", Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru.
Angela
A
Privat
Instituto de Medicina Tropical "Alexander von Humboldt", Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru.
Maria
M
Cruz
Institut de Recherche pour le Développement, UMR177 IRD/CIRAD «INTERTRYP», Montpellier, France.
Julie
J
Pagniez
BVT-VIRBAC, La Seyne sur Mer, France.
Gérard-Marie
GM
Papierok
Laboratory of Transmission, Control and Immunobiology of Infection, LR11-IPT-02, Institut Pasteur de Tunis, Tunis, Tunisie.
Faten Bel Haj
FB
Rhouma
Centro de Transfusión de la Comunidad de Madrid, Madrid, Spain.
Pilar
P
Torres
Institut de Recherche pour le Développement, UMR177 IRD/CIRAD «INTERTRYP», Montpellier, France.
Jean-Loup
JL
Lemesre
Laboratory of Medical Parasitology, Biotechnology and Biomolecules, LR11-IPT-06, Institut Pasteur de Tunis, Tunis, Tunisia.
Mehdi
M
Chenik
Laboratory of Medical Parasitology, Biotechnology and Biomolecules, LR11-IPT-06, Institut Pasteur de Tunis, Tunis, Tunisia.
Amel
A
Meddeb-Garnaoui
D056704:Adaptive Immunity; D000818:Animals; D000953:Antigens, Protozoan / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology*; D000954:Antigens, Surface / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology; D053804:Granzymes / Q000097:blood; D006801:Humans; D056724:Immunity, Humoral; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007891:Leishmania / Q000276:immunology*; D007896:Leishmaniasis / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D010641:Phenotype; D016052:Protozoan Vaccines / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology*; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D016052:Protozoan Vaccines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D053804:Granzymes