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https://www.arca.fiocruz.br/handle/icict/51455
α-GAL IMMUNIZATION POSITIVELY IMPACTS TRYPANOSOMA CRUZI COLONIZATION OF HEART TISSUE IN A MOUSE MODEL
Author
Cunha, Gisele Macêdo Rodrigues da
Nogueira, Denise Silva
Chunga, Juan Atilio Jimenez
Galvão, Lucia Maria da Cunha
Chiari, Egler
Brito, Carlos Ramon Nascimento
Soares, Rodrigo Pedro Pinto
Nogueira, Paula Monalisa
Fujiwara, Ricardo Toshio
Hincapie, Robert
Chaves, Carlos-Sanhueza
Oliveira, Fabricio Marcus Silva
Marques, Alexandre Ferreira
Nogueira, Denise Silva
Chunga, Juan Atilio Jimenez
Galvão, Lucia Maria da Cunha
Chiari, Egler
Brito, Carlos Ramon Nascimento
Soares, Rodrigo Pedro Pinto
Nogueira, Paula Monalisa
Fujiwara, Ricardo Toshio
Hincapie, Robert
Chaves, Carlos-Sanhueza
Oliveira, Fabricio Marcus Silva
Marques, Alexandre Ferreira
Affilliation
Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil
Universidad San Martin de Porres. Lima, Peru
Universidad Nacional Mayor de San Marcos. Faculdad de Ciencias Biologicas. Escuela Profesional de Microbiología y Parasitología. Laboratorio de Parasitología en Fauna Silvestre y Zoonosis. Lima, Peru
Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil
Universidade Federal do Rio Grande do Norte. Centro de Ciências da Saúde. Departamento de Análises Clínicas e Toxicológicas. Natal, RN, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil
School of Chemistry and Biochemistry. School of Biological Sciences. Georgia Institute of Technology. Atlanta, GA, United States of America
School of Chemistry and Biochemistry. School of Biological Sciences. Georgia Institute of Technology. Atlanta, GA, United States of America
School of Chemistry and Biochemistry. School of Biological Sciences. Georgia Institute of Technology. Atlanta, GA, United States of America
Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil
Universidad San Martin de Porres. Lima, Peru
Universidad Nacional Mayor de San Marcos. Faculdad de Ciencias Biologicas. Escuela Profesional de Microbiología y Parasitología. Laboratorio de Parasitología en Fauna Silvestre y Zoonosis. Lima, Peru
Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil
Universidade Federal do Rio Grande do Norte. Centro de Ciências da Saúde. Departamento de Análises Clínicas e Toxicológicas. Natal, RN, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil
School of Chemistry and Biochemistry. School of Biological Sciences. Georgia Institute of Technology. Atlanta, GA, United States of America
School of Chemistry and Biochemistry. School of Biological Sciences. Georgia Institute of Technology. Atlanta, GA, United States of America
School of Chemistry and Biochemistry. School of Biological Sciences. Georgia Institute of Technology. Atlanta, GA, United States of America
Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil
Abstract
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a significant endemic infectious disease in Latin America and is spreading in the U.S. and Europe with the presence of its insect transmission vector. No approved vaccine against Chagas disease exists. We describe a vaccine candidate based on a carbohydrate found on the T. cruzi cell surface, linked in the vaccine to a virus-like particle that provides a strong and focused immune response. Mice were immunized and challenged with the Trypanosoma cruzi parasites from two strains (Y and Colombian). Vaccination conferred substantial protection of mice against infection, compared with the unvaccinated group. Vaccinated animals presented low parasitemia, increased production of pro-inflammatory cytokines IL-12 and IFN-gamma, decreased cardiomyocyte damage, and rapid clearance of parasite nests from heart tissue. These effects were especially significant at time points modeling chronic disease, an important consideration for this pathogen. We, therefore, believe this is a valuable path to pursue in the development of vaccines against Chagas disease. Chagas disease, caused by the parasite Trypanosoma cruzi, is considered endemic in more than 20 countries but lacks both an approved vaccine and limited treatment for its chronic stage. Chronic infection is most harmful to human health because of long-term parasitic infection of the heart. Here we show that immunization with a virus-like particle vaccine displaying a high density of the immunogenic alpha-Gal trisaccharide (Q beta-alpha Gal) induced several beneficial effects concerning acute and chronic T. cruzi infection in alpha 1,3-galactosyltransferase knockout mice. Approximately 60% of these animals were protected from initial infection with high parasite loads. Vaccinated animals also produced high anti-alpha Gal IgG antibody titers, improved IFN-gamma and IL-12 cytokine production, and controlled parasitemia in the acute phase at 8 days post-infection (dpi) for the Y strain and 22 dpi for the Colombian strain. In the chronic stage of infection (36 and 190 dpi, respectively), all of the vaccinated group survived, showing significantly decreased heart inflammation and clearance of amastigote nests from the heart tissue.
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