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

• Published in: Frontiers in immunology Vol. 10; p. 813
• Main Author: Palatnik-de-Sousa, Clarisa Beatriz
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 16.04.2019
• Subjects: cutaneous leishmaniasis vaccines; Immunology; Leishmune® vaccine; multi-epitope vaccines; nucleoside hydrolases; visceral leishmaniasis vaccines; nucleoside hydrolases; multi-epitope vaccines; Leishmune® vaccine; cutaneous leishmaniasis vaccines; visceral leishmaniasis vaccines
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.00813

NH36 is a vital enzyme of the DNA metabolism and a specific target for anti- chemotherapy. We developed second-generation vaccines composed of the FML complex or its main native antigen, the NH36 nucleoside hydrolase of and saponin, and a DNA vaccine containing the NH36 gene. All these vaccines were effective in prophylaxis and treatment of mice and dog visceral leishmaniasis (VL). The FML-saponin vaccine became the first licensed veterinary vaccine against leishmaniasis (Leishmune®) which reduced the incidence of human and canine VL in endemic areas. The NH36, DNA or recombinant protein vaccines induced a Th1 CD4 IFN-γ mediated protection in mice. Efficacy against VL was mediated by a CD4 TNF-α T lymphocyte response against the NH36-F3 domain, while against tegumentary leishmaniasis (TL) a CD8 T lymphocyte response to F1 was also required. These domains were 36-41 % more protective than NH36, and a recombinant F1F3 chimera was 21% stronger than the domains, promoting a 99.8% reduction of the parasite load. We also identified the most immunogenic NH36 domains and epitopes for PBMC of active human VL, cured or asymptomatic and DTH patients. Currently, the NH36 subunit recombinant vaccine is turning into a multi-epitope T cell synthetic vaccine against VL and TL.