title: Immunogenicity of HSP-70, KMP-11 and PFR-2 leishmanial antigens in the experimental model of canine visceral leishmaniasis.
abstract: Zoonotic visceral leishmaniasis (ZVL) is a parasitic disease caused by Leishmania infantum/L. chagasi that is emerging as an important medical and veterinary problem. Dogs are the domestic reservoir for this parasite and, therefore, the main target for controlling the transmission to humans. In the present work, we have evaluated the immunogenicity of the Leishmania infantum heat shock protein (HSP)-70, paraflagellar rod protein (PFR)-2 and kinetoplastida membrane protein (KMP)-11 recombinant proteins in dogs experimentally infected with the parasite. We have shown that peripheral blood mononuclear cells (PBMC) from experimentally infected dogs proliferated in response to these recombinant antigens and against the soluble leishmanial antigen (SLA). We have also quantified the mRNA expression level of the cytokines induced in PBMC upon stimulation with the HSP-70, PFR-2 and KMP-11 proteins. These recombinant proteins induced an up-regulation of IFN-gamma. HSP-70 and PFR-2 also produced an increase of the TNF-alpha transcripts abundance. No measurable induction of IL-10 was observed and low levels of IL-4 mRNA were produced in response to the three mentioned recombinant antigens. Serum levels of specific antibodies against HSP-70, PFR-2 and KMP-11 recombinant proteins were also determined in these animals. Our study showed that HSP-70, KMP-11 and PFR-2 proteins are recognized by infected canines. Furthermore, these antigens produce a Th1-type immune response, suggesting that they may be involved in protection. The identification as vaccine candidates of Leishmania antigens that elicit appropriate immune responses in the canine model is a key step in the rational approach to generate a vaccine for canine visceral leishmaniasis.
authors.affiliation: WHO Collaborating Centre for Leishmaniasis, Centro Nacional de Microbiología, Inst. de Salud Carlos III, Majadahonda, Spain.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Carrillo
authors.forename: Martín
authors.initials: M
authors.lastname: Crusat
authors.forename: Javier
authors.initials: J
authors.lastname: Nieto
authors.forename: Carmen
authors.initials: C
authors.lastname: Chicharro
authors.forename: Maria del Carmen
authors.initials: Mdel C
authors.lastname: Thomas
authors.forename: Enrique
authors.initials: E
authors.lastname: Martínez
authors.forename: Basilio
authors.initials: B
authors.lastname: Valladares
authors.forename: Carmen
authors.initials: C
authors.lastname: Cañavate
authors.forename: Jose María
authors.initials: JM
authors.lastname: Requena
authors.forename: Manuel Carlos
authors.initials: MC
authors.lastname: López
authors.forename: Jorge
authors.initials: J
authors.lastname: Alvar
authors.forename: Javier
authors.initials: J
authors.lastname: Moreno
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004285:Dogs; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D018314:Leishmania infantum / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000517:prevention & control*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D054332:Leishmaniasis Vaccines; C105582:PFR-2 protein, Leishmania; D015800:Protozoan Proteins; D011994:Recombinant Proteins