Nucleoside Hydrolase NH 36: A Vital Enzyme for the Leishmania Genus in the Development of T-Cell Epitope Cross-Protective Vaccines
NH36 is a vital enzyme of the DNA metabolism and a specific target for anti-Leishmania chemotherapy. We developed second-generation vaccines composed of the FML complex or its main native antigen, the NH36 nucleoside hydrolase of Leishmania (L.) donovani and saponin, and a DNA vaccine containing the...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00813/full |
| _version_ | 1818020198428442624 |
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| author | Clarisa Beatriz Palatnik-de-Sousa Clarisa Beatriz Palatnik-de-Sousa |
| author_facet | Clarisa Beatriz Palatnik-de-Sousa Clarisa Beatriz Palatnik-de-Sousa |
| author_sort | Clarisa Beatriz Palatnik-de-Sousa |
| collection | DOAJ |
| description | NH36 is a vital enzyme of the DNA metabolism and a specific target for anti-Leishmania chemotherapy. We developed second-generation vaccines composed of the FML complex or its main native antigen, the NH36 nucleoside hydrolase of Leishmania (L.) donovani 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. |
| first_indexed | 2024-04-14T08:01:50Z |
| format | Article |
| id | doaj.art-f8412a11382a47698d773855e95e575c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T08:01:50Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f8412a11382a47698d773855e95e575c2022-12-22T02:04:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-04-011010.3389/fimmu.2019.00813442101Nucleoside Hydrolase NH 36: A Vital Enzyme for the Leishmania Genus in the Development of T-Cell Epitope Cross-Protective VaccinesClarisa Beatriz Palatnik-de-Sousa0Clarisa Beatriz Palatnik-de-Sousa1Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilFaculty of Medicine, Institute for Research in Immunology, University of São Paulo, São Paulo, BrazilNH36 is a vital enzyme of the DNA metabolism and a specific target for anti-Leishmania chemotherapy. We developed second-generation vaccines composed of the FML complex or its main native antigen, the NH36 nucleoside hydrolase of Leishmania (L.) donovani 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.00813/fullvisceral leishmaniasis vaccinescutaneous leishmaniasis vaccinesnucleoside hydrolasesmulti-epitope vaccinesLeishmune® vaccine |
| spellingShingle | Clarisa Beatriz Palatnik-de-Sousa Clarisa Beatriz Palatnik-de-Sousa Nucleoside Hydrolase NH 36: A Vital Enzyme for the Leishmania Genus in the Development of T-Cell Epitope Cross-Protective Vaccines Frontiers in Immunology visceral leishmaniasis vaccines cutaneous leishmaniasis vaccines nucleoside hydrolases multi-epitope vaccines Leishmune® vaccine |
| title | Nucleoside Hydrolase NH 36: A Vital Enzyme for the Leishmania Genus in the Development of T-Cell Epitope Cross-Protective Vaccines |
| title_full | Nucleoside Hydrolase NH 36: A Vital Enzyme for the Leishmania Genus in the Development of T-Cell Epitope Cross-Protective Vaccines |
| title_fullStr | Nucleoside Hydrolase NH 36: A Vital Enzyme for the Leishmania Genus in the Development of T-Cell Epitope Cross-Protective Vaccines |
| title_full_unstemmed | Nucleoside Hydrolase NH 36: A Vital Enzyme for the Leishmania Genus in the Development of T-Cell Epitope Cross-Protective Vaccines |
| title_short | Nucleoside Hydrolase NH 36: A Vital Enzyme for the Leishmania Genus in the Development of T-Cell Epitope Cross-Protective Vaccines |
| title_sort | nucleoside hydrolase nh 36 a vital enzyme for the leishmania genus in the development of t cell epitope cross protective vaccines |
| topic | visceral leishmaniasis vaccines cutaneous leishmaniasis vaccines nucleoside hydrolases multi-epitope vaccines Leishmune® vaccine |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00813/full |
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