Development of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis.

Visceral leishmaniasis (VL) is a vector-borne disease affecting humans and domestic animals that constitutes a serious public health problem in many countries. Although many antigens have been examined so far as protein- or DNA-based vaccines, none of them conferred complete long-term protection. Th...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Noushin Saljoughian, Tahereh Taheri, Farnaz Zahedifard, Yasaman Taslimi, Fatemeh Doustdari, Azam Bolhassani, Delaram Doroud, Hiva Azizi, Kazem Heidari, Mohammad Vasei, Nabiollah Namvar Asl, Barbara Papadopoulou, Sima Rafati
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/499954bbfcd346d18bbb91fe41e99e56
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:499954bbfcd346d18bbb91fe41e99e56
record_format	dspace
spelling	oai:doaj.org-article:499954bbfcd346d18bbb91fe41e99e562021-11-18T09:15:08ZDevelopment of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis.1935-27271935-273510.1371/journal.pntd.0002174https://doaj.org/article/499954bbfcd346d18bbb91fe41e99e562013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23638195/pdf/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Visceral leishmaniasis (VL) is a vector-borne disease affecting humans and domestic animals that constitutes a serious public health problem in many countries. Although many antigens have been examined so far as protein- or DNA-based vaccines, none of them conferred complete long-term protection. The use of the lizard non-pathogenic to humans Leishmania (L.) tarentolae species as a live vaccine vector to deliver specific Leishmania antigens is a recent approach that needs to be explored further. In this study, we evaluated the effectiveness of live vaccination in protecting BALB/c mice against L. infantum infection using prime-boost regimens, namely Live/Live and DNA/Live. As a live vaccine, we used recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinases (CPA and CPB without its unusual C-terminal extension (CPB(-CTE))) as a tri-fusion gene. For DNA priming, the tri-fusion gene was encoded in pcDNA formulated with cationic solid lipid nanoparticles (cSLN) acting as an adjuvant. At different time points post-challenge, parasite burden and histopathological changes as well as humoral and cellular immune responses were assessed. Our results showed that immunization with both prime-boost A2-CPA-CPB(-CTE)-recombinant L. tarentolae protects BALB/c mice against L. infantum challenge. This protective immunity is associated with a Th1-type immune response due to high levels of IFN-γ production prior and after challenge and with lower levels of IL-10 production after challenge, leading to a significantly higher IFN-γ/IL-10 ratio compared to the control groups. Moreover, this immunization elicited high IgG1 and IgG2a humoral immune responses. Protection in mice was also correlated with a high nitric oxide production and low parasite burden. Altogether, these results indicate the promise of the A2-CPA-CPB(-CTE)-recombinant L. tarentolae as a safe live vaccine candidate against VL.Noushin SaljoughianTahereh TaheriFarnaz ZahedifardYasaman TaslimiFatemeh DoustdariAzam BolhassaniDelaram DoroudHiva AziziKazem HeidariMohammad VaseiNabiollah Namvar AslBarbara PapadopoulouSima RafatiPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 7, Iss 4, p e2174 (2013)
institution	DOAJ
collection	DOAJ
language	EN
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 Saljoughian Tahereh Taheri Farnaz Zahedifard Yasaman Taslimi Fatemeh Doustdari Azam Bolhassani Delaram Doroud Hiva Azizi Kazem Heidari Mohammad Vasei Nabiollah Namvar Asl Barbara Papadopoulou Sima Rafati Development of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis.
description	Visceral leishmaniasis (VL) is a vector-borne disease affecting humans and domestic animals that constitutes a serious public health problem in many countries. Although many antigens have been examined so far as protein- or DNA-based vaccines, none of them conferred complete long-term protection. The use of the lizard non-pathogenic to humans Leishmania (L.) tarentolae species as a live vaccine vector to deliver specific Leishmania antigens is a recent approach that needs to be explored further. In this study, we evaluated the effectiveness of live vaccination in protecting BALB/c mice against L. infantum infection using prime-boost regimens, namely Live/Live and DNA/Live. As a live vaccine, we used recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinases (CPA and CPB without its unusual C-terminal extension (CPB(-CTE))) as a tri-fusion gene. For DNA priming, the tri-fusion gene was encoded in pcDNA formulated with cationic solid lipid nanoparticles (cSLN) acting as an adjuvant. At different time points post-challenge, parasite burden and histopathological changes as well as humoral and cellular immune responses were assessed. Our results showed that immunization with both prime-boost A2-CPA-CPB(-CTE)-recombinant L. tarentolae protects BALB/c mice against L. infantum challenge. This protective immunity is associated with a Th1-type immune response due to high levels of IFN-γ production prior and after challenge and with lower levels of IL-10 production after challenge, leading to a significantly higher IFN-γ/IL-10 ratio compared to the control groups. Moreover, this immunization elicited high IgG1 and IgG2a humoral immune responses. Protection in mice was also correlated with a high nitric oxide production and low parasite burden. Altogether, these results indicate the promise of the A2-CPA-CPB(-CTE)-recombinant L. tarentolae as a safe live vaccine candidate against VL.
format	article
author	Noushin Saljoughian Tahereh Taheri Farnaz Zahedifard Yasaman Taslimi Fatemeh Doustdari Azam Bolhassani Delaram Doroud Hiva Azizi Kazem Heidari Mohammad Vasei Nabiollah Namvar Asl Barbara Papadopoulou Sima Rafati
author_facet	Noushin Saljoughian Tahereh Taheri Farnaz Zahedifard Yasaman Taslimi Fatemeh Doustdari Azam Bolhassani Delaram Doroud Hiva Azizi Kazem Heidari Mohammad Vasei Nabiollah Namvar Asl Barbara Papadopoulou Sima Rafati
author_sort	Noushin Saljoughian
title	Development of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis.
title_short	Development of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis.
title_full	Development of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis.
title_fullStr	Development of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis.
title_full_unstemmed	Development of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis.
title_sort	development of novel prime-boost strategies based on a tri-gene fusion recombinant l. tarentolae vaccine against experimental murine visceral leishmaniasis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/499954bbfcd346d18bbb91fe41e99e56
work_keys_str_mv	AT noushinsaljoughian developmentofnovelprimebooststrategiesbasedonatrigenefusionrecombinantltarentolaevaccineagainstexperimentalmurinevisceralleishmaniasis AT taherehtaheri developmentofnovelprimebooststrategiesbasedonatrigenefusionrecombinantltarentolaevaccineagainstexperimentalmurinevisceralleishmaniasis AT farnazzahedifard developmentofnovelprimebooststrategiesbasedonatrigenefusionrecombinantltarentolaevaccineagainstexperimentalmurinevisceralleishmaniasis AT yasamantaslimi developmentofnovelprimebooststrategiesbasedonatrigenefusionrecombinantltarentolaevaccineagainstexperimentalmurinevisceralleishmaniasis AT fatemehdoustdari developmentofnovelprimebooststrategiesbasedonatrigenefusionrecombinantltarentolaevaccineagainstexperimentalmurinevisceralleishmaniasis AT azambolhassani developmentofnovelprimebooststrategiesbasedonatrigenefusionrecombinantltarentolaevaccineagainstexperimentalmurinevisceralleishmaniasis AT delaramdoroud developmentofnovelprimebooststrategiesbasedonatrigenefusionrecombinantltarentolaevaccineagainstexperimentalmurinevisceralleishmaniasis AT hivaazizi developmentofnovelprimebooststrategiesbasedonatrigenefusionrecombinantltarentolaevaccineagainstexperimentalmurinevisceralleishmaniasis AT kazemheidari developmentofnovelprimebooststrategiesbasedonatrigenefusionrecombinantltarentolaevaccineagainstexperimentalmurinevisceralleishmaniasis AT mohammadvasei developmentofnovelprimebooststrategiesbasedonatrigenefusionrecombinantltarentolaevaccineagainstexperimentalmurinevisceralleishmaniasis AT nabiollahnamvarasl developmentofnovelprimebooststrategiesbasedonatrigenefusionrecombinantltarentolaevaccineagainstexperimentalmurinevisceralleishmaniasis AT barbarapapadopoulou developmentofnovelprimebooststrategiesbasedonatrigenefusionrecombinantltarentolaevaccineagainstexperimentalmurinevisceralleishmaniasis AT simarafati developmentofnovelprimebooststrategiesbasedonatrigenefusionrecombinantltarentolaevaccineagainstexperimentalmurinevisceralleishmaniasis
_version_	1718420901033148416

Development of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis.

Ejemplares similares