A dual drug sensitive L. major induces protection without lesion in C57BL/6 mice.
Leishmaniasis is a major health problem in some endemic areas and yet, no vaccine is available against any form of the disease. Historically, leishmanization (LZ) which is an inoculation of individual with live Leishmania, is the most effective control measure at least against cutaneous leishmaniasi...
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ftdoajarticles:oai:doaj.org/article:386cbc88288c46ecb4c891557063e24b 2023-05-15T15:12:25+02:00 A dual drug sensitive L. major induces protection without lesion in C57BL/6 mice. Noushin Davoudi Ali Khamesipour Fereidoun Mahboudi W Robert McMaster 2014-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002785 https://doaj.org/article/386cbc88288c46ecb4c891557063e24b EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4038489?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002785 https://doaj.org/article/386cbc88288c46ecb4c891557063e24b PLoS Neglected Tropical Diseases, Vol 8, Iss 5, p e2785 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002785 2023-01-08T01:27:34Z Leishmaniasis is a major health problem in some endemic areas and yet, no vaccine is available against any form of the disease. Historically, leishmanization (LZ) which is an inoculation of individual with live Leishmania, is the most effective control measure at least against cutaneous leishmaniasis (CL). Due to various reasons, LZ is not used today. Several live attenuated Leishmania have been developed but their use is limited. Previously, we developed a transgenic strain of L. major that harbors two suicide genes tk and cd genes (lmtkcd+/+) for use as a challenge strain in vaccine studies. These genes render the parasite susceptible to Ganciclovir (GCV) and 5-flurocytosine (5-FC). The dual drug sensitive strain of L. major was developed using gene targeting technology using a modified Herpes Simplex Virus thymidine kinase gene (hsv-tk) sensitive to Ganciclovir antibiotic and Saccharomyces cerevisae cytosine deaminase gene (cd sensitive to 5-flurocytosine) that were stably introduced into L. major chromosome. BALB/c mice inoculated with lmtkcd+/+ developed lesions which upon treatment with GCV and 5-FC completely healed. In the current study, the transgenic lmtkcd+/+strain was assessed as a live vaccine model to determine the time necessary to develop a protective immune response. C57BL/6 mice were inoculated with the transgenic lmtkcd+/+strain, and treated at the time of inoculation (day 0) or at day 8 after inoculation. Immunized animals were challenged with wild-type L. major, and complete protection was induced in mice that were treated at day 8. The results show that in contrast to leishmanization, in group of mice inoculated with a dual sensitive L. major development and persistence of lesion is not necessary to induce Th1 response and protection. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 5 e2785 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Noushin Davoudi Ali Khamesipour Fereidoun Mahboudi W Robert McMaster A dual drug sensitive L. major induces protection without lesion in C57BL/6 mice. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Leishmaniasis is a major health problem in some endemic areas and yet, no vaccine is available against any form of the disease. Historically, leishmanization (LZ) which is an inoculation of individual with live Leishmania, is the most effective control measure at least against cutaneous leishmaniasis (CL). Due to various reasons, LZ is not used today. Several live attenuated Leishmania have been developed but their use is limited. Previously, we developed a transgenic strain of L. major that harbors two suicide genes tk and cd genes (lmtkcd+/+) for use as a challenge strain in vaccine studies. These genes render the parasite susceptible to Ganciclovir (GCV) and 5-flurocytosine (5-FC). The dual drug sensitive strain of L. major was developed using gene targeting technology using a modified Herpes Simplex Virus thymidine kinase gene (hsv-tk) sensitive to Ganciclovir antibiotic and Saccharomyces cerevisae cytosine deaminase gene (cd sensitive to 5-flurocytosine) that were stably introduced into L. major chromosome. BALB/c mice inoculated with lmtkcd+/+ developed lesions which upon treatment with GCV and 5-FC completely healed. In the current study, the transgenic lmtkcd+/+strain was assessed as a live vaccine model to determine the time necessary to develop a protective immune response. C57BL/6 mice were inoculated with the transgenic lmtkcd+/+strain, and treated at the time of inoculation (day 0) or at day 8 after inoculation. Immunized animals were challenged with wild-type L. major, and complete protection was induced in mice that were treated at day 8. The results show that in contrast to leishmanization, in group of mice inoculated with a dual sensitive L. major development and persistence of lesion is not necessary to induce Th1 response and protection. |
format |
Article in Journal/Newspaper |
author |
Noushin Davoudi Ali Khamesipour Fereidoun Mahboudi W Robert McMaster |
author_facet |
Noushin Davoudi Ali Khamesipour Fereidoun Mahboudi W Robert McMaster |
author_sort |
Noushin Davoudi |
title |
A dual drug sensitive L. major induces protection without lesion in C57BL/6 mice. |
title_short |
A dual drug sensitive L. major induces protection without lesion in C57BL/6 mice. |
title_full |
A dual drug sensitive L. major induces protection without lesion in C57BL/6 mice. |
title_fullStr |
A dual drug sensitive L. major induces protection without lesion in C57BL/6 mice. |
title_full_unstemmed |
A dual drug sensitive L. major induces protection without lesion in C57BL/6 mice. |
title_sort |
dual drug sensitive l. major induces protection without lesion in c57bl/6 mice. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0002785 https://doaj.org/article/386cbc88288c46ecb4c891557063e24b |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 5, p e2785 (2014) |
op_relation |
http://europepmc.org/articles/PMC4038489?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002785 https://doaj.org/article/386cbc88288c46ecb4c891557063e24b |
op_doi |
https://doi.org/10.1371/journal.pntd.0002785 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
8 |
container_issue |
5 |
container_start_page |
e2785 |
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1766343102055841792 |