title: Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis.
abstract: 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.
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, 69 Pasteur Ave., Tehran, 13164, Iran; Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Shahbazi
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, 69 Pasteur Ave., Tehran, 13164, Iran.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Zahedifard
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, 69 Pasteur Ave., Tehran, 13164, Iran.
authors.forename: Tahereh
authors.initials: T
authors.lastname: Taheri
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, 69 Pasteur Ave., Tehran, 13164, Iran.
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Taslimi
authors.affiliation: Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Jamshidi
authors.affiliation: Department of Molecular and Cytopathology, Daneshbod Pathology Laboratory, Shiraz, Iran.
authors.forename: Sadegh
authors.initials: S
authors.lastname: Shirian
authors.affiliation: Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Niousha
authors.initials: N
authors.lastname: Mahdavi
authors.affiliation: Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hassankhani
authors.affiliation: Department of Molecular and Cytopathology, Daneshbod Pathology Laboratory, Shiraz, Iran.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Daneshbod
authors.affiliation: Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Sayyed Hamid
authors.initials: SH
authors.lastname: Zarkesh-Esfahani
authors.affiliation: Research Center in Infectious Diseases, CHU de Québec Research Center and Department of Microbiology, Infectious Disease and Immunology, Laval University, Quebec, QC, Canada.
authors.forename: Barbara
authors.initials: B
authors.lastname: Papadopoulou
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, 69 Pasteur Ave., Tehran, 13164, Iran.
authors.forename: Sima
authors.initials: S
authors.lastname: Rafati
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics* / Q000276:immunology; D002478:Cells, Cultured; D057056:Cysteine Proteases / Q000235:genetics* / Q000276:immunology; D004283:Dog Diseases / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D004285:Dogs; D005260:Female; D015870:Gene Expression; D056724:Immunity, Humoral; D007891:Leishmania / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000517:prevention & control* / Q000662:veterinary*; D008297:Male; D014611:Vaccination / Q000379:methods / Q000662:veterinary; D014613:Vaccines, Attenuated / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use
chemical_list: D000953:Antigens, Protozoan; D054332:Leishmaniasis Vaccines; D014613:Vaccines, Attenuated; D057056:Cysteine Proteases