Transmission blocking sugar baits for the control of Leishmania development inside sand flies using environmentally friendly beta-glycosides and their aglycones

Submitted by Sandra Infurna ([email protected]) on 2019-01-22T11:07:33Z No. of bitstreams: 1 taina_ferreira_etal_IOC_2018.pdf: 2753184 bytes, checksum: 0ca1961c8eb592f5d2c86f13873c692d (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-01-22T11:18:03Z (GMT) No. of bitstreams: 1 taina_ferreira_etal_IOC_2018.pdf: 2753184 bytes, checksum: 0ca1961c8eb592f5d2c86f13873c692d (MD5)Made available in DSpace on 2019-01-22T11:18:03Z (GMT). No. of bitstreams: 1 taina_ferreira_etal_IOC_2018.pdf: 2753184 bytes, checksum: 0ca1961c8eb592f5d2c86f13873c692d (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica e Fisiologia de Insetos. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular de Doenças Endêmicas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica e Fisiologia de Insetos. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Doenças Parasitarias. Rio de Janeiro, RJ. Brasil / Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica e Fisiologia de Insetos. Rio de Janeiro, RJ. Brasil.University of Glasgow. Wellcome Centre for Molecular Parasitology. Glasgow, UK / El Colegio de la Frontera Sur. Unidad Villahermosa, Mexico.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica e Fisiologia de Insetos. Rio de Janeiro, RJ. Brasil / Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular. Rio de Janeiro, RJ, Brasil.The sand fly Lutzomyia longipalpis is the main vector of American visceral leishmaniasis, a disease caused by parasites of the genus Leishmania. Adults of this insect feed on blood (females only) or sugar from plant sources, but their digestion of carbohydrates is poorly studied. Beta-glycosides as esculin and amygdalin are plant compounds and release toxic compounds as esculetin and mandelonitrile when hydrolyzed. Beta-glucosidase and trehalase are essential enzymes in sand fly metabolism and participate in sugar digestion. It is therefore possible that the toxic portions of these glycosides, released during digestion, affect sand fly physiology and the development of Leishmania

TcVac1 vaccine delivery by intradermal electroporation enhances vaccine induced immune protection against Trypanosoma cruzi infection in mice

Trabajo de investigación doctoral de Wael Hegazy Hassan Moustafa bajo la dirección de Juan Carlos Vázquez ChagoyánThe efforts for the development and testing of vaccines against Trypanosoma cruzi infection have increased during the past years. We have designed a TcVac series of vaccines composed of T. cruzi derived, GPI-anchored membrane antigens. The TcVac vaccines have been shown to elicit humoral and cellular mediated immune responses and provide significant (but not complete) control of experimental infection in mice and dogs. Herein, we aimed to test two immunization protocols for the delivery of DNA-prime/ DNA-boost vaccine (TcVac1) composed of TcG2 and TcG4 antigens in a BALB/c mouse model. Mice were immunized with TcVac1 through intradermal/electroporation (IDE) or intramuscular (IM) routes, challenged with T. cruzi, and evaluated during acute phase of infection. The humoral immune response was evaluated through the assessment of anti-TcG2 and anti-TcG4 IgG subtypes by using an ELISA. Cellular immune response was assessed through a lymphocyte proliferation assay. Finally, clinical and morphopathological aspects were evaluated for all experimental animals. Our results demonstrated that when comparing TcVac1 IDE delivery vs IM delivery, the former induced significantly higher level of antigen-specific antibody response (IgG2a + IgG2b > IgG1) and lymphocyte proliferation, which expanded in response to challenge infection. Histological evaluation after challenge infection showed infiltration of inflammatory cells (macrophages and lymphocytes) in the heart and skeletal tissue of all infected mice. However, the largest increase in inflammatory infiltrate was observed in TcVac1_IDE/Tc mice when compared with TcVac1_IM/Tc or non-vaccinated/infected mice. The extent of tissue inflammatory infiltrate was directly associated with the control of tissue amastigote nests in vaccinated/ infected (vs. non-vaccinated/infected) mice. Our results suggest that IDE delivery improves the protective efficacy of TcVac1 vaccine against T. cruzi infection in mice when compared with IM delivery of the vaccine.Universidad Autónoma de Estado de México (proyecto No. 3326/2012C), Consejo Nacional de Ciencia y Tecnología (Proyecto No. 156701) . Beca CONACyT a M.Sc. Wael Hegazy Hassan Moustafa (Beca numero No. 518232/291117)