C-terminal domain deletion enhances the protective activity of cpa/cpb loaded solid lipid nanoparticles against Leishmania major in BALB/c mice.
BACKGROUND:We have demonstrated that vaccination with pDNA encoding cysteine proteinase Type II (CPA) and Type I (CPB) with its unusual C-terminal extension (CTE) can partially protect BALB/c mice against cutaneous leishmanial infection. Unfortunately, this protection is insufficient to completely c...
Published in: | PLoS Neglected Tropical Diseases |
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Online Access: | https://doi.org/10.1371/journal.pntd.0001236 https://doaj.org/article/f84e2a71cb0d407f82976fc9ed6e9d5f |
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ftdoajarticles:oai:doaj.org/article:f84e2a71cb0d407f82976fc9ed6e9d5f 2023-05-15T15:14:16+02:00 C-terminal domain deletion enhances the protective activity of cpa/cpb loaded solid lipid nanoparticles against Leishmania major in BALB/c mice. Delaram Doroud Farnaz Zahedifard Alireza Vatanara Yasaman Taslimi Rouholah Vahabpour Fatemeh Torkashvand Behrooz Vaziri Abdolhossein Rouholamini Najafabadi Sima Rafati 2011-07-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001236 https://doaj.org/article/f84e2a71cb0d407f82976fc9ed6e9d5f EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3134432?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001236 https://doaj.org/article/f84e2a71cb0d407f82976fc9ed6e9d5f PLoS Neglected Tropical Diseases, Vol 5, Iss 7, p e1236 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001236 2022-12-30T20:49:54Z BACKGROUND:We have demonstrated that vaccination with pDNA encoding cysteine proteinase Type II (CPA) and Type I (CPB) with its unusual C-terminal extension (CTE) can partially protect BALB/c mice against cutaneous leishmanial infection. Unfortunately, this protection is insufficient to completely control infection without booster injection. Furthermore, in developing vaccines for leishmaniasis, it is necessary to consider a proper adjuvant and/or delivery system to promote an antigen specific immune response. Solid lipid nanoparticles have found their way in drug delivery system development against intracellular infections and cancer, but not Leishmania DNA vaccination. Therefore, undefined effect of cationic solid lipid nanoparticles (cSLN) as an adjuvant in enhancing the immune response toward leishmanial antigens led us to refocus our vaccine development projects. METHODOLOGY/PRINCIPAL FINDINGS:Three pDNAs encoding L. major cysteine proteinase type I and II (with or without CTE) were formulated by cSLN. BALB/c mice were immunized twice by 3-week interval, with cSLN-pcDNA-cpa/b, pcDNA-cpa/b, cSLN-pcDNA-cpa/b(-CTE), pcDNA-cpa/b(-CTE), cSLN, cSLN-pcDNA and PBS. Mice vaccinated with cSLN-pcDNA-cpa/b(-CTE) showed significantly higher levels of parasite inhibition related to protection with specific Th1 immune response development, compared to other groups. Parasite inhibition was determined by different techniques currently available in exploration vacciation efficacy, i.e., flowcytometry on footpad and lymph node, footpad caliper based measurements and imaging as well as lymph node microtitration assay. Among these techniques, lymph node flowcytometry was found to be the most rapid, sensitive and easily reproducible method for discrimination between the efficacy of vaccination strategies. CONCLUSIONS/SIGNIFICANCE:This report demonstrates cSLN's ability to boost immune response magnitude of cpa/cpb(-CTE) cocktail vaccination against leishmaniasis so that the average parasite inhibition percent could be increased ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 5 7 e1236 |
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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 Delaram Doroud Farnaz Zahedifard Alireza Vatanara Yasaman Taslimi Rouholah Vahabpour Fatemeh Torkashvand Behrooz Vaziri Abdolhossein Rouholamini Najafabadi Sima Rafati C-terminal domain deletion enhances the protective activity of cpa/cpb loaded solid lipid nanoparticles against Leishmania major in BALB/c mice. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:We have demonstrated that vaccination with pDNA encoding cysteine proteinase Type II (CPA) and Type I (CPB) with its unusual C-terminal extension (CTE) can partially protect BALB/c mice against cutaneous leishmanial infection. Unfortunately, this protection is insufficient to completely control infection without booster injection. Furthermore, in developing vaccines for leishmaniasis, it is necessary to consider a proper adjuvant and/or delivery system to promote an antigen specific immune response. Solid lipid nanoparticles have found their way in drug delivery system development against intracellular infections and cancer, but not Leishmania DNA vaccination. Therefore, undefined effect of cationic solid lipid nanoparticles (cSLN) as an adjuvant in enhancing the immune response toward leishmanial antigens led us to refocus our vaccine development projects. METHODOLOGY/PRINCIPAL FINDINGS:Three pDNAs encoding L. major cysteine proteinase type I and II (with or without CTE) were formulated by cSLN. BALB/c mice were immunized twice by 3-week interval, with cSLN-pcDNA-cpa/b, pcDNA-cpa/b, cSLN-pcDNA-cpa/b(-CTE), pcDNA-cpa/b(-CTE), cSLN, cSLN-pcDNA and PBS. Mice vaccinated with cSLN-pcDNA-cpa/b(-CTE) showed significantly higher levels of parasite inhibition related to protection with specific Th1 immune response development, compared to other groups. Parasite inhibition was determined by different techniques currently available in exploration vacciation efficacy, i.e., flowcytometry on footpad and lymph node, footpad caliper based measurements and imaging as well as lymph node microtitration assay. Among these techniques, lymph node flowcytometry was found to be the most rapid, sensitive and easily reproducible method for discrimination between the efficacy of vaccination strategies. CONCLUSIONS/SIGNIFICANCE:This report demonstrates cSLN's ability to boost immune response magnitude of cpa/cpb(-CTE) cocktail vaccination against leishmaniasis so that the average parasite inhibition percent could be increased ... |
format |
Article in Journal/Newspaper |
author |
Delaram Doroud Farnaz Zahedifard Alireza Vatanara Yasaman Taslimi Rouholah Vahabpour Fatemeh Torkashvand Behrooz Vaziri Abdolhossein Rouholamini Najafabadi Sima Rafati |
author_facet |
Delaram Doroud Farnaz Zahedifard Alireza Vatanara Yasaman Taslimi Rouholah Vahabpour Fatemeh Torkashvand Behrooz Vaziri Abdolhossein Rouholamini Najafabadi Sima Rafati |
author_sort |
Delaram Doroud |
title |
C-terminal domain deletion enhances the protective activity of cpa/cpb loaded solid lipid nanoparticles against Leishmania major in BALB/c mice. |
title_short |
C-terminal domain deletion enhances the protective activity of cpa/cpb loaded solid lipid nanoparticles against Leishmania major in BALB/c mice. |
title_full |
C-terminal domain deletion enhances the protective activity of cpa/cpb loaded solid lipid nanoparticles against Leishmania major in BALB/c mice. |
title_fullStr |
C-terminal domain deletion enhances the protective activity of cpa/cpb loaded solid lipid nanoparticles against Leishmania major in BALB/c mice. |
title_full_unstemmed |
C-terminal domain deletion enhances the protective activity of cpa/cpb loaded solid lipid nanoparticles against Leishmania major in BALB/c mice. |
title_sort |
c-terminal domain deletion enhances the protective activity of cpa/cpb loaded solid lipid nanoparticles against leishmania major in balb/c mice. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doi.org/10.1371/journal.pntd.0001236 https://doaj.org/article/f84e2a71cb0d407f82976fc9ed6e9d5f |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 5, Iss 7, p e1236 (2011) |
op_relation |
http://europepmc.org/articles/PMC3134432?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001236 https://doaj.org/article/f84e2a71cb0d407f82976fc9ed6e9d5f |
op_doi |
https://doi.org/10.1371/journal.pntd.0001236 |
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PLoS Neglected Tropical Diseases |
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5 |
container_issue |
7 |
container_start_page |
e1236 |
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