title: Enhanced protective efficacy of nonpathogenic recombinant leishmania tarentolae expressing cysteine proteinases combined with a sand fly salivary antigen.
abstract: BACKGROUND
  Novel vaccination approaches are needed to prevent leishmaniasis. Live attenuated vaccines are the gold standard for protection against intracellular pathogens such as Leishmania and there have been new developments in this field. The nonpathogenic to humans lizard protozoan parasite, Leishmania (L) tarentolae, has been used effectively as a vaccine platform against visceral leishmaniasis in experimental animal models. Correspondingly, pre-exposure to sand fly saliva or immunization with a salivary protein has been shown to protect mice against cutaneous leishmaniasis.
  
  
  RESULTS
  Here, we tested the efficacy of a novel combination of established protective parasite antigens expressed by L. tarentolae together with a sand fly salivary antigen as a vaccine strategy against L. major infection. The immunogenicity and protective efficacy of different DNA/Live and Live/Live prime-boost vaccination modalities with live recombinant L. tarentolae stably expressing cysteine proteinases (type I and II, CPA/CPB) and PpSP15, an immunogenic salivary protein from Phlebotomus papatasi, a natural vector of L. major, were tested both in susceptible BALB/c and resistant C57BL/6 mice. Both humoral and cellular immune responses were assessed before challenge and at 3 and 10 weeks after Leishmania infection. In both strains of mice, the strongest protective effect was observed when priming with PpSP15 DNA and boosting with PpSP15 DNA and live recombinant L. tarentolae stably expressing cysteine proteinase genes.
  
  
  CONCLUSIONS
  The present study is the first to use a combination of recombinant L. tarentolae with a sand fly salivary antigen (PpSP15) and represents a novel promising vaccination approach against leishmaniasis.
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Zahedifard
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Gholami
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Tahereh
authors.initials: T
authors.lastname: Taheri
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Taslimi
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Doustdari
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Negar
authors.initials: N
authors.lastname: Seyed
authors.affiliation: Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Torkashvand
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, Maryland, United States of America.
authors.forename: Claudio
authors.initials: C
authors.lastname: Meneses
authors.affiliation: Research Centre in Infectious Disease, CHUL Research Centre (CHU de Québec Research Centre) and Department of Microbiology, Infectious Disease and Immunology, Laval University, Quebec, Canada.
authors.forename: Barbara
authors.initials: B
authors.lastname: Papadopoulou
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, Maryland, United States of America.
authors.forename: Shaden
authors.initials: S
authors.lastname: Kamhawi
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, Maryland, United States of America.
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Valenzuela
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Sima
authors.initials: S
authors.lastname: Rafati
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D057056:Cysteine Proteases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007891:Leishmania / Q000276:immunology*; D007896:Leishmaniasis / Q000517:prevention & control; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011576:Psychodidae; D012471:Salivary Proteins and Peptides / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D054332:Leishmaniasis Vaccines; D012471:Salivary Proteins and Peptides; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D057056:Cysteine Proteases