3 years ago

Phlebotomus papatasi yellow-related and apyrase salivary proteins are candidates for vaccination against human cutaneous leishmaniasis.

Wafa Kammoun-Rebai, Nabil Belhadj Hmida, Emna Chabaane, Aymen Tlili, Jesus G Valenzuela, Fabiano Oliveira, Hechmi Louzir, Melika Ben Ahmed, Rahma Sakkouhi, Soumaya Marzouki, Shaden Kamhawi, Maha Abdeladhim
Nowadays, there is no available vaccine for human leishmaniasis. Animal experiments demonstrate that pre-exposure to sand fly saliva confers protection against leishmaniasis. Our preceding work in humans indicates that Phlebotomus (P) papatasi saliva, induce the production of IL-10 by CD8+ T lymphocytes. The neutralization of IL-10 enhanced the activation of a T cells CD4+ population producing IFN-γ. Herein, we used a biochemical and functional genomics approach to identify the sand fly salivary components that are responsible for the activation of the Th1 immune response in humans therefore constituting potential vaccine candidates against leishmaniasis. Fractionated Phlebotomus papatasi salivary extracts were first tested on T lymphocytes of immune donors. We confirmed that the CD4+ lymphocytes proliferate and produce IFN-γ in response to stimulation with the proteins of a molecular weight > 30 KDa. Peripheral blood mononuclear cells from immune donors were transfected with plasmids coding for the most abundant proteins from P. papatasi salivary gland cDNA library. Our result showed that the "yellow related proteins", PPTSP42 and PPTSP44, and "apyrase", PPTSP36, are the proteins responsible for the aforementioned cellular immune response and IFN-γ-production. Strikingly, PPTSP44 triggered the highest level of lymphocyte proliferation and IFN-γ production. Multiplex cytokine analysis confirmed the Th1-polarized response induced by these proteins. Importantly, recombinant PPTSP44 validated the results observed with the DNA plasmid, further supporting that PPTSP44 constitutes a promising vaccine candidate against human leishmaniasis.

Publisher URL: http://doi.org/10.1016/j.jid.2017.09.043

DOI: 10.1016/j.jid.2017.09.043

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