title: Coadministration of the Three Antigenic Leishmania infantum Poly (A) Binding Proteins as a DNA Vaccine Induces Protection against Leishmania major Infection in BALB/c Mice.
abstract: BACKGROUND
  Highly conserved intracellular proteins from Leishmania have been described as antigens in natural and experimental infected mammals. The present study aimed to evaluate the antigenicity and prophylactic properties of the Leishmania infantum Poly (A) binding proteins (LiPABPs).
  
  
  RESULTS
  Three different members of the LiPABP family have been described. Recombinant tools based on these proteins were constructed: recombinant proteins and DNA vaccines. The three recombinant proteins were employed for coating ELISA plates. Sera from human and canine patients of visceral leishmaniasis and human patients of mucosal leishmaniasis recognized the three LiPABPs. In addition, the protective efficacy of a DNA vaccine based on the combination of the three Leishmania PABPs has been tested in a model of progressive murine leishmaniasis: BALB/c mice infected with Leishmania major. The induction of a Th1-like response against the LiPABP family by genetic vaccination was able to down-regulate the IL-10 predominant responses elicited by parasite LiPABPs after infection in this murine model. This modulation resulted in a partial protection against L. major infection. LiPABP vaccinated mice showed a reduction on the pathology that was accompanied by a decrease in parasite burdens, in antibody titers against Leishmania antigens and in the IL-4 and IL-10 parasite-specific mediated responses in comparison to control mice groups immunized with saline or with the non-recombinant plasmid.
  
  
  CONCLUSIONS
  The results presented here demonstrate for the first time the prophylactic properties of a new family of Leishmania antigenic intracellular proteins, the LiPABPs. The redirection of the immune response elicited against the LiPABP family (from IL-10 towards IFN-γ mediated responses) by genetic vaccination was able to induce a partial protection against the development of the disease in a highly susceptible murine model of leishmaniasis.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Soto
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Corvo
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Garde
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Ramírez
authors.affiliation: LeishmanCeres Laboratory (GLP Compliance Certified), Parasitology Unit. Veterinary Faculty, University of Extremadura, Cáceres, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Iniesta
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Bonay
authors.affiliation: LeishmanCeres Laboratory (GLP Compliance Certified), Parasitology Unit. Veterinary Faculty, University of Extremadura, Cáceres, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gómez-Nieto
authors.affiliation: Departamento de Bioquímica-Investigación, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Víctor M
authors.initials: VM
authors.lastname: González
authors.affiliation: Departamento de Bioquímica-Investigación, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: M Elena
authors.initials: ME
authors.lastname: Martín
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Alonso
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Eduardo A F
authors.initials: EA
authors.lastname: Coelho
authors.affiliation: Centro de Pesquisas Gonçalo Moniz (Fundação Oswaldo Cruz-FIOCRUZ), Salvador, Bahia, Brazil.
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.affiliation: Centro de Pesquisas Gonçalo Moniz (Fundação Oswaldo Cruz-FIOCRUZ), Salvador, Bahia, Brazil.
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
authors.affiliation: Immunobiology of Inflammation Laboratory, Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Iborra
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D018314:Leishmania infantum / Q000276:immunology*; 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; D008807:Mice, Inbred BALB C; D039102:Poly(A)-Binding Proteins / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D002352:Carrier Proteins; D016207:Cytokines; D054332:Leishmaniasis Vaccines; D039102:Poly(A)-Binding Proteins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma