title: Development of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis.
abstract: 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.
authors: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors: Noushin
authors: N
authors: Saljoughian
authors: Tahereh
authors: T
authors: Taheri
authors: Farnaz
authors: F
authors: Zahedifard
authors: Yasaman
authors: Y
authors: Taslimi
authors: Fatemeh
authors: F
authors: Doustdari
authors: Azam
authors: A
authors: Bolhassani
authors: Delaram
authors: D
authors: Doroud
authors: Hiva
authors: H
authors: Azizi
authors: Kazem
authors: K
authors: Heidari
authors: Mohammad
authors: M
authors: Vasei
authors: Nabiollah
authors: N
authors: Namvar Asl
authors: Barbara
authors: B
authors: Papadopoulou
authors: Sima
authors: S
authors: Rafati
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D005260:Female; D050939:Gene Fusion / Q000235:genetics; D056724:Immunity, Humoral / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D016052:Protozoan Vaccines / Q000627:therapeutic use*; D019444:Vaccines, DNA / Q000627:therapeutic use*; D014614:Vaccines, Synthetic / Q000627:therapeutic use*
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D016753:Interleukin-10; D007371:Interferon-gamma
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