Nucleoside Hydrolase NH 36: A Vital Enzyme for the Leishmania Genus in the Development of T-Cell Epitope Cross-Protective Vaccines

Conclusions Nucleoside hydrolases are vital enzymes for the replication of Leishmania, conserved phylogenetic marker of the genus and strong-specific immunogens. We demonstrated that NH36 is an excellent target for chemotherapy of visceral leishmaniasis. Searching for the most immunogenic fraction of promastigotes of Leishmania we described the FML antigen of L. (L.) donovani, that has as its main component, the NH36 Nucleoside hydrolase. We developed second–generation vaccines with the FML and the NH36 native antigens, and with the NH36 recombinant protein. In addition, we obtained a third generation vaccine based upon the NH36 gene. All these vaccines were protective and curative when assayed in the murine and canine models of leishmaniasis, and the FML-vaccine called Leishmune® reduced the incidence of human and canine disease in the endemic areas. Recently we initiate the search for the most immunogenic part of the NH36 sequence aiming to optimize the vaccine efficacy. We observed that the F3 vaccine has an important role in signaling the optimal control of visceral leishmaniasis in mice and that the F1 domain is also needed for protection against tegumentary leishmaniasis. This knowledge allowed us to develop a recombinant chimera vaccine, which optimized the vaccine efficacy. Furthermore, aiming to develop a potential T-cell epitope synthetic vaccine against both human visceral and cutaneous leishmaniasis we identified the major immunogenic regions of NH36 re...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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