CpG ODN D35 improves the response to abbreviated low-dose pentavalent antimonial treatment in non-human primate model of cutaneous leishmaniasis.
Cutaneous leishmaniasis (CL) affects the lives of 0.7-1 million people every year causing lesions that take months to heal. These lesions can result in disfiguring scars with psychological, social and economic consequences. Antimonials are the first line of therapy for CL, however the treatment is l...
Published in: | PLOS Neglected Tropical Diseases |
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2020
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ftdoajarticles:oai:doaj.org/article:d7284f9e62384f2481e13e85f6fb0f68 2023-05-15T15:13:24+02:00 CpG ODN D35 improves the response to abbreviated low-dose pentavalent antimonial treatment in non-human primate model of cutaneous leishmaniasis. Seth G Thacker Ian L McWilliams Beatrice Bonnet Lydia Halie Serge Beaucage Swaksha Rachuri Ranadhir Dey Robert Duncan Farrokh Modabber Stephen Robinson Graeme Bilbe Byron Arana Daniela Verthelyi 2020-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008050 https://doaj.org/article/d7284f9e62384f2481e13e85f6fb0f68 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008050 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008050 https://doaj.org/article/d7284f9e62384f2481e13e85f6fb0f68 PLoS Neglected Tropical Diseases, Vol 14, Iss 2, p e0008050 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008050 2022-12-31T07:16:57Z Cutaneous leishmaniasis (CL) affects the lives of 0.7-1 million people every year causing lesions that take months to heal. These lesions can result in disfiguring scars with psychological, social and economic consequences. Antimonials are the first line of therapy for CL, however the treatment is lengthy and linked to significant toxicities; further, its efficacy is variable and resistant parasites are emerging. Shorter or lower dose antimonial treatment regimens, which would decrease the risk of adverse events and improve patient compliance, have shown reduced efficacy and further increase the risk emergence of antimonial-resistant strains. The progression of lesions in CL is partly determined by the immune response it elicits, and previous studies showed that administration of immunomodulatory type D CpG ODNs, magnifies the immune response to Leishmania and reduces lesion severity in nonhuman primates (NHP) challenged with Leishmania major or Leishmania amazonensis. Here we explored whether the addition of a single dose of immunomodulating CpG ODN D35 augments the efficacy of a short-course, low-dose pentavalent antimonial treatment regimen. Results show that macaques treated with D35 plus 5mg/kg sodium stibogluconate (SbV) for 10 days had smaller lesions and reduced time to re-epithelization after infection with Leishmania major. No toxicities were evident during the studies, even at doses of D35 10 times higher than those used in treatment. Critically, pentavalent antimonial treatment did not modify the ability of D35 to induce type I IFNs. The findings support the efficacy of D35 as adjuvant therapy for shorter, low dose pentavalent antimonial treatment. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 14 2 e0008050 |
institution |
Open Polar |
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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 Seth G Thacker Ian L McWilliams Beatrice Bonnet Lydia Halie Serge Beaucage Swaksha Rachuri Ranadhir Dey Robert Duncan Farrokh Modabber Stephen Robinson Graeme Bilbe Byron Arana Daniela Verthelyi CpG ODN D35 improves the response to abbreviated low-dose pentavalent antimonial treatment in non-human primate model of cutaneous leishmaniasis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Cutaneous leishmaniasis (CL) affects the lives of 0.7-1 million people every year causing lesions that take months to heal. These lesions can result in disfiguring scars with psychological, social and economic consequences. Antimonials are the first line of therapy for CL, however the treatment is lengthy and linked to significant toxicities; further, its efficacy is variable and resistant parasites are emerging. Shorter or lower dose antimonial treatment regimens, which would decrease the risk of adverse events and improve patient compliance, have shown reduced efficacy and further increase the risk emergence of antimonial-resistant strains. The progression of lesions in CL is partly determined by the immune response it elicits, and previous studies showed that administration of immunomodulatory type D CpG ODNs, magnifies the immune response to Leishmania and reduces lesion severity in nonhuman primates (NHP) challenged with Leishmania major or Leishmania amazonensis. Here we explored whether the addition of a single dose of immunomodulating CpG ODN D35 augments the efficacy of a short-course, low-dose pentavalent antimonial treatment regimen. Results show that macaques treated with D35 plus 5mg/kg sodium stibogluconate (SbV) for 10 days had smaller lesions and reduced time to re-epithelization after infection with Leishmania major. No toxicities were evident during the studies, even at doses of D35 10 times higher than those used in treatment. Critically, pentavalent antimonial treatment did not modify the ability of D35 to induce type I IFNs. The findings support the efficacy of D35 as adjuvant therapy for shorter, low dose pentavalent antimonial treatment. |
format |
Article in Journal/Newspaper |
author |
Seth G Thacker Ian L McWilliams Beatrice Bonnet Lydia Halie Serge Beaucage Swaksha Rachuri Ranadhir Dey Robert Duncan Farrokh Modabber Stephen Robinson Graeme Bilbe Byron Arana Daniela Verthelyi |
author_facet |
Seth G Thacker Ian L McWilliams Beatrice Bonnet Lydia Halie Serge Beaucage Swaksha Rachuri Ranadhir Dey Robert Duncan Farrokh Modabber Stephen Robinson Graeme Bilbe Byron Arana Daniela Verthelyi |
author_sort |
Seth G Thacker |
title |
CpG ODN D35 improves the response to abbreviated low-dose pentavalent antimonial treatment in non-human primate model of cutaneous leishmaniasis. |
title_short |
CpG ODN D35 improves the response to abbreviated low-dose pentavalent antimonial treatment in non-human primate model of cutaneous leishmaniasis. |
title_full |
CpG ODN D35 improves the response to abbreviated low-dose pentavalent antimonial treatment in non-human primate model of cutaneous leishmaniasis. |
title_fullStr |
CpG ODN D35 improves the response to abbreviated low-dose pentavalent antimonial treatment in non-human primate model of cutaneous leishmaniasis. |
title_full_unstemmed |
CpG ODN D35 improves the response to abbreviated low-dose pentavalent antimonial treatment in non-human primate model of cutaneous leishmaniasis. |
title_sort |
cpg odn d35 improves the response to abbreviated low-dose pentavalent antimonial treatment in non-human primate model of cutaneous leishmaniasis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008050 https://doaj.org/article/d7284f9e62384f2481e13e85f6fb0f68 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 2, p e0008050 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008050 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008050 https://doaj.org/article/d7284f9e62384f2481e13e85f6fb0f68 |
op_doi |
https://doi.org/10.1371/journal.pntd.0008050 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
14 |
container_issue |
2 |
container_start_page |
e0008050 |
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1766343955221315584 |