title: Recombinant Leishmania tarentolae expressing the A2 virulence gene as a novel candidate vaccine against visceral leishmaniasis.
abstract: Visceral leishmaniasis is the most severe form of leishmaniasis. To date, there is no effective vaccine against this disease. Many antigens have been examined so far as protein- or DNA-based vaccines, but none of them conferred complete long-term protection. The use of live attenuated vaccines has recently emerged as a promising vaccination strategy. In this study, we stably expressed the Leishmania donovani A2 antigen in Leishmania tarentolae, a non-pathogenic member of the genus Leishmania, and evaluated its protective efficacy as a live vaccine against L. infantum challenge. Our results show that a single intraperitoneal administration of the A2-recombinant L. tarentolae strain protects BALB/c mice against L. infantum challenge and that protective immunity is associated with high levels of IFN-gamma production prior and after challenge. This is accompanied by reduced levels of IL-5 production after challenge, leading to a potent Th1 immune response. In contrast, intravenous injection elicited a Th2 type response, characterized by higher levels of IL-5 and high humoral immune response, resulting in a less efficient protection. All together, these results indicate the promise of A2-expressing L. tarentolae as a safe live vaccine against visceral leishmaniasis.
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Mizbani
authors.forename: Tahereh
authors.initials: T
authors.lastname: Taheri
authors.forename: Farnaz
authors.initials: F
authors.lastname: Zahedifard
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Taslimi
authors.forename: Hiva
authors.initials: H
authors.lastname: Azizi
authors.forename: Kayhan
authors.initials: K
authors.lastname: Azadmanesh
authors.forename: Barbara
authors.initials: B
authors.lastname: Papadopoulou
authors.forename: Sima
authors.initials: S
authors.lastname: Rafati
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D016054:DNA, Protozoan / Q000302:isolation & purification; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000276:immunology; D015848:Interleukin-5 / Q000235:genetics; D054332:Leishmaniasis Vaccines / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000517:prevention & control*; D017737:Macrophages, Peritoneal / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells
chemical_list: C107645:A2 protein, Leishmania donovani; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D015848:Interleukin-5; D054332:Leishmaniasis Vaccines; D015800:Protozoan Proteins; D007371:Interferon-gamma