Induction of immunogenicity by live attenuated Leishmania donovani centrin deleted parasites in dogs |
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Authors: | Jacqueline Araújo Fiuza Helton da Costa Santiago Angamuthu Selvapandiyan Sreenivas Gannavaram Natasha Delaqua Ricci Lilian Lacerda Bueno Daniella Castanheira Bartholomeu Rodrigo Correa-Oliveira Hira Lal Nakhasi Ricardo Toshio Fujiwara |
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Institution: | 1. Laboratory of Cellular and Molecular Immunology, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil;2. Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;3. Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA;4. Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;5. Institute of Molecular Medicine, 254 Okhla Industrial Estate, Phase III, New Delhi 110020, India |
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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. |
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Keywords: | Canine visceral leishmaniasis Vaccine Attenuated parasite |
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