Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis.
Canine Visceral Leishmaniasis (CVL) is a major veterinary and public health problem caused by Leishmania infantum (L. infantum) in many endemic countries. It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is o...
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doaj-49f6c42154df4873b0680fc82ba5205b2020-11-24T21:32:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e013279410.1371/journal.pone.0132794Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis.Mehdi ShahbaziFarnaz ZahedifardTahereh TaheriYasaman TaslimiShahram JamshidiSadegh ShirianNiousha MahdaviMehdi HassankhaniYahya DaneshbodSayyed Hamid Zarkesh-EsfahaniBarbara PapadopoulouSima RafatiCanine Visceral Leishmaniasis (CVL) is a major veterinary and public health problem caused by Leishmania infantum (L. infantum) in many endemic countries. It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is often fatal when left untreated. Control of VL in dogs would dramatically decrease infection pressure of L. infantum for humans, since dogs are the main domestic reservoir. In the past decade, various subunits and DNA antigens have been identified as potential vaccine candidates in experimental animal models, but none has been approved for human use so far. In this study, we vaccinated outbreed dogs with a prime-boost regimen based on recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinase genes (CPA and CPB without its unusual C-terminal extension (CPB-CTE) and evaluated its immunogenicity and protective immunity against L. infantum infectious challenge. We showed that vaccinated animals produced significantly higher levels of IgG2, but not IgG1, and also IFN-γ and TNF-α, but low IL-10 levels, before and after challenge as compared to control animals. Protection in dogs was also correlated with a strong DTH response and low parasite burden in the vaccinated group. Altogether, immunization with recombinant L. tarentolae A2-CPA-CPB-CTE was proven to be immunogenic and induced partial protection in dogs, hence representing a promising live vaccine candidate against CVL.http://europepmc.org/articles/PMC4509652?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mehdi Shahbazi Farnaz Zahedifard Tahereh Taheri Yasaman Taslimi Shahram Jamshidi Sadegh Shirian Niousha Mahdavi Mehdi Hassankhani Yahya Daneshbod Sayyed Hamid Zarkesh-Esfahani Barbara Papadopoulou Sima Rafati |
spellingShingle |
Mehdi Shahbazi Farnaz Zahedifard Tahereh Taheri Yasaman Taslimi Shahram Jamshidi Sadegh Shirian Niousha Mahdavi Mehdi Hassankhani Yahya Daneshbod Sayyed Hamid Zarkesh-Esfahani Barbara Papadopoulou Sima Rafati Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis. PLoS ONE |
author_facet |
Mehdi Shahbazi Farnaz Zahedifard Tahereh Taheri Yasaman Taslimi Shahram Jamshidi Sadegh Shirian Niousha Mahdavi Mehdi Hassankhani Yahya Daneshbod Sayyed Hamid Zarkesh-Esfahani Barbara Papadopoulou Sima Rafati |
author_sort |
Mehdi Shahbazi |
title |
Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis. |
title_short |
Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis. |
title_full |
Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis. |
title_fullStr |
Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis. |
title_full_unstemmed |
Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis. |
title_sort |
evaluation of live recombinant nonpathogenic leishmania tarentolae expressing cysteine proteinase and a2 genes as a candidate vaccine against experimental canine visceral leishmaniasis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
Canine Visceral Leishmaniasis (CVL) is a major veterinary and public health problem caused by Leishmania infantum (L. infantum) in many endemic countries. It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is often fatal when left untreated. Control of VL in dogs would dramatically decrease infection pressure of L. infantum for humans, since dogs are the main domestic reservoir. In the past decade, various subunits and DNA antigens have been identified as potential vaccine candidates in experimental animal models, but none has been approved for human use so far. In this study, we vaccinated outbreed dogs with a prime-boost regimen based on recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinase genes (CPA and CPB without its unusual C-terminal extension (CPB-CTE) and evaluated its immunogenicity and protective immunity against L. infantum infectious challenge. We showed that vaccinated animals produced significantly higher levels of IgG2, but not IgG1, and also IFN-γ and TNF-α, but low IL-10 levels, before and after challenge as compared to control animals. Protection in dogs was also correlated with a strong DTH response and low parasite burden in the vaccinated group. Altogether, immunization with recombinant L. tarentolae A2-CPA-CPB-CTE was proven to be immunogenic and induced partial protection in dogs, hence representing a promising live vaccine candidate against CVL. |
url |
http://europepmc.org/articles/PMC4509652?pdf=render |
work_keys_str_mv |
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