In Vitro Evaluation of a Soluble Leishmania Promastigote Surface Antigen as a Potential Vaccine Candidate against Human Leishmaniasis

Rym Chamakh-Ayari (1) , Rachel Bras-Gonçalves (2) , Narges Bahi-Jaber (3, 4) , Elodie Petitdidier (2) , Wafa Markikou-Ouni (1) , Karim Aoun (1) , Javier Moreno (5) , Eugenia Carrillo (5) , Poonam Salotra (6) , Himanshu Kaushal (6) , Narender Singh Negi (6) , Jorge Arevalo (7) , Francesca Falconi-Agapito (7) , Angela Privat (7) , Maria Cruz (7) , Julie Pagniez (2) , Gerard-Marie Papierok (8) , Faten Belhaj Rhouma (3) , Pilar Torres (9) , Jean-Loup Lemesre (2) , Mehdi Chenik (1) , Amel Meddeb-Garnaoui (1)

1 LR11IPT06 - Laboratoire de Parasitologie Médicale, Biotechnologies et Biomolécules
2 UMR INTERTRYP - Interactions hôtes-vecteurs-parasites-environnement dans les maladies tropicales négligées dues aux trypanosomatides
3 LR11IPT02 - Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection
4 EGEAL - Expression de Gènes et régulation Epigénétique par l'ALiment
5 WHO Collaborating Center for Leishmaniasis, Centro Nacional de Microbiologia
6 ICMR - National Institute of Pathology
7 IMT AvH - Instituto de Medicina Tropical "Alexander von Humboldt"
8 BVT-VIRBAC, La Seyne sur Mer, France
9 Centro de Transfusión de la Comunidad de Madrid, Madrid, Spain

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-c 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-c, granzyme B and IL- 10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-a 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-c after LaPSA-38S stimulation, in CCLm. A high positive correlation was observed between the percentage of IFN-c-producing CD4+ T cells and the released IFN-c. 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

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Microbiology and Parasitology; Parasitology; Life Sciences [q-bio]; Immunology; Vaccinology

Rym Chamakh-Ayari, Rachel Bras-Gonçalves, Narges Bahi-Jaber, Elodie Petitdidier, Wafa Markikou-Ouni, et al.. In Vitro Evaluation of a Soluble Leishmania Promastigote Surface Antigen as a Potential Vaccine Candidate against Human Leishmaniasis. PLoS ONE, 2014, 9 (5), pp.e92708. ⟨10.1371/journal.pone.0092708⟩. ⟨pasteur-01098532⟩