title: Cross-protective effect of a combined L5 plus L3 Leishmania major ribosomal protein based vaccine combined with a Th1 adjuvant in murine cutaneous and visceral leishmaniasis.
abstract: BACKGROUND
  Two Leishmania major ribosomal proteins L3 (LmL3) and L5 (LmL5) have been described as protective molecules against cutaneous leishmaniasis due to infection with L. major and Leishmania braziliensis in BALB/c mice when immunized with a Th1 adjuvant (non-methylated CpG-oligodeoxynucleotides; CpG-ODN). In the present study we analyzed the cross-protective efficacy of an LmL3-LmL5-CpG ODN combined vaccine against infection with Leishmania amazonensis and Leishmania chagasi (syn. Leishmania infantum) the etiologic agents of different clinical forms of human leishmaniasis in South America.
  
  
  METHODS
  The combined vaccine was administered subcutaneously to BALB/c mice. After immunization the cellular and humoral responses elicited were analyzed. Mice were independently challenged with L. amazonensis and L. chagasi. The size of the cutaneous lesions caused by the infection with the first species, the parasite loads and the immune response in both infection models were analyzed nine weeks after challenge.
  
  
  RESULTS
  Mice vaccinated with the combined vaccine showed a Th1-like response against LmL3 and LmL5. Vaccinated mice were able to delay lesion development due to L. amazonensis infection and to control parasite loads in the site of infection. A reduction of the parasite burden in the lymph nodes draining the site of infection and in the liver and spleen was observed in the vaccinated mice after a subcutaneous infection with L. chagasi. In both models of infection, protection was correlated to parasite antigen-specific production of IFN-γ and down-regulation of parasite-mediated IL-4 and IL-10 responses.
  
  
  CONCLUSIONS
  The data presented here demonstrate the potential use of L. major L3 and L5 recombinant ribosomal proteins for the development of vaccines against various Leishmania species.
authors.forename: Laura
authors.initials: L
authors.lastname: Ramirez
authors.forename: Laura
authors.initials: L
authors.lastname: Corvo
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Duarte
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Chávez-Fumagalli
authors.forename: Diogo G
authors.initials: DG
authors.lastname: Valadares
authors.forename: Diego M
authors.initials: DM
authors.lastname: Santos
authors.forename: Camila I
authors.initials: CI
authors.lastname: de Oliveira
authors.forename: Marta R
authors.initials: MR
authors.lastname: Escutia
authors.forename: Carlos
authors.initials: C
authors.lastname: Alonso
authors.forename: Pedro
authors.initials: P
authors.lastname: Bonay
authors.forename: Carlos A P
authors.initials: CA
authors.lastname: Tavares
authors.forename: Eduardo A F
authors.initials: EA
authors.lastname: Coelho
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Departamento de Biología Molecular, Nicolás Cabrera 1, Universidad Autónoma de Madrid, 28049 Madrid, Spain. msoto@cbm.uam.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: Soto
mesh_terms: D000818:Animals; D003429:Cross Reactions / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D018320:Leishmania major / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D009838:Oligodeoxyribonucleotides; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: C408982:CPG-oligonucleotide; D016207:Cytokines; D054332:Leishmaniasis Vaccines; D009838:Oligodeoxyribonucleotides; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; C029742:ribosomal protein L5