title: Induction of immunogenicity by live attenuated Leishmania donovani centrin deleted parasites in dogs.
abstract: Zoonotic visceral leishmaniasis, caused by the intracellular protozoan parasite Leishmania infantum, is a neglected tropical disease that is often fatal when untreated. Dogs are considered the main reservoir of L. infantum in zoonotic VL as the presence of infected dogs may increase the risk for human infection. Canine visceral leishmaniasis (CVL) is a major veterinary and public health problem in Southern Europe, Middle East and South America. Control of animal reservoirs relies on elimination of seropositive dogs in endemic areas. However, treatment of infected dogs is not considered a favorable approach as this can lead to emergence of drug resistance since the same drugs are used to treat human infections. Therefore, vaccination against CVL remains the best alternative in control of the animal reservoirs. In this study, we present data on the immunogenicity profile of a live attenuated parasite LdCen(-/-) in a canine infection model and compared it to that of Leishmune(®), a commercially available recombinant vaccine. The immunogenicity of the LdCen(-/-) parasites was evaluated by antibody secretion, production of intracytoplasmic and secreted cytokines, activation and proliferation of T cells. Vaccination with LdCen(-/-) resulted in high immunogenicity as revealed by the higher IgGTotal, IgG1, and IgG2 production and higher lymphoproliferative response. Further, LdCen(-/-) vaccinated dogs showed higher frequencies of activated CD4+ and CD8+ T cells, IFN-γ production by CD8+ T cells, increased secretion of TNF-α and IL-12/IL-23p40 and decreased secretion of IL-4. These results contribute to the understanding of immunogenicity elicited by live attenuated L. donovani parasites and, consequently, to the development of effective vaccines against visceral leishmaniasis.
authors: Laboratory of Cellular and Molecular Immunology, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
authors: Jacqueline Araújo
authors: JA
authors: Fiuza
authors: Helton da Costa
authors: Hda C
authors: Santiago
authors: Angamuthu
authors: A
authors: Selvapandiyan
authors: Sreenivas
authors: S
authors: Gannavaram
authors: Natasha Delaqua
authors: ND
authors: Ricci
authors: Lilian Lacerda
authors: LL
authors: Bueno
authors: Daniella Castanheira
authors: DC
authors: Bartholomeu
authors: Rodrigo
authors: R
authors: Correa-Oliveira
authors: Hira Lal
authors: HL
authors: Nakhasi
authors: Ricardo Toshio
authors: RT
authors: Fujiwara
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002135:Calcium-Binding Proteins / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D016207:Cytokines / Q000276:immunology; D004283:Dog Diseases / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D004285:Dogs; D007893:Leishmania donovani / Q000235:genetics / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000469:parasitology / Q000662:veterinary*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D002135:Calcium-Binding Proteins; D002868:Chromosomal Proteins, Non-Histone; D016207:Cytokines; D054332:Leishmaniasis Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; C056608:caltractin