| Author | Portillo, Susana | |
| Author | Zepeda, Brenda G. | |
| Author | Iniguez, Eva | |
| Author | Olivas, Janet J. | |
| Author | Karimi, Nasim H. | |
| Author | Moreira, Octacilio C. | |
| Author | Marques, Alexandre F, | |
| Author | Michael, Katja | |
| Author | Maldonado, Rosa A. | |
| Author | Almeida, Igor C. | |
| Access date | 2019-08-27T16:41:42Z | |
| Available date | 2019-08-27T16:41:42Z | |
| Document date | 2019 | |
| Citation | PORTILLO, Susana et al. A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease. Vaccines, n. 13, p. 1-15, 2019. | pt_BR |
| ISSN | 2076-393X | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/35123 | |
| Language | eng | pt_BR |
| Publisher | MDPI | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Glicovacina profilática | pt_BR |
| Subject in Portuguese | α-Gal | pt_BR |
| Subject in Portuguese | Doença de Chagas aguda | pt_BR |
| Subject in Portuguese | Proteção | pt_BR |
| Title | A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease | pt_BR |
| Type | Article | |
| DOI | 10.1038/s41541-019-0107-7 | pt_BR |
| Abstract | Chagas disease (ChD), caused by the hemoflagellate parasite Trypanosoma cruzi, affects six to seven million people in Latin America.
Lately, it has become an emerging public health concern in nonendemic regions such as North America and Europe. There is no
prophylactic or therapeutic vaccine as yet, and current chemotherapy is rather toxic and has limited efficacy in the chronic phase of
the disease. The parasite surface is heavily coated by glycoproteins such as glycosylphosphatidylinositol (GPI)-anchored mucins
(tGPI-mucins), which display highly immunogenic terminal nonreducing α-galactopyranosyl (α-Gal)-containing glycotopes that are
entirely absent in humans. The immunodominant tGPI-mucin α-Gal glycotope, the trisaccharide Galα1,3Galβ1,4GlcNAc (Galα3LN),
elicits high levels of protective T. cruzi-specific anti-α-Gal antibodies in ChD patients in both the acute and chronic phases. Although
glycoconjugates are the major parasite glycocalyx antigens, they remain completely unexplored as potential ChD vaccine
candidates. Here we investigate the efficacy of the T. cruzi immunodominant glycotope Galα3LN, covalently linked to a carrier
protein (human serum albumin (HSA)), as a prophylactic vaccine candidate in the acute model of ChD, using the α1,3-
galactosyltransferase-knockout (α1,3GalT-KO) mouse, which mimics the human immunoresponse to α-Gal glycotopes. Animals
vaccinated with Galα3LN-HSA were fully protected against lethal T. cruzi challenge by inducing a strong anti-α-Gal antibodymediated
humoral response. Furthermore, Galα3LN-HSA-vaccinated α1,3GalT-KO mice exhibited significant reduction (91.7–99.9%)
in parasite load in all tissues analyzed, cardiac inflammation, myocyte necrosis, and T cell infiltration. This is a proof-of-concept
study to demonstrate the efficacy of a prophylactic α-Gal-based glycovaccine for experimental acute Chagas disease. | pt_BR |
| Affilliation | The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA. | pt_BR |
| Affilliation | The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA. | pt_BR |
| Affilliation | The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA. | pt_BR |
| Affilliation | The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA. | pt_BR |
| Affilliation | The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | The University of Texas at El Paso. Border Biomedical Research Center. Department of Chemistry and Biochemistry. El Paso, TX, USA. | pt_BR |
| Affilliation | The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA. | pt_BR |
| Affilliation | The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA. | pt_BR |
| Subject | Prophylactic α-Gal-based glycovaccine | pt_BR |
| Subject | Chagas Disease | pt_BR |
| Subject | Murine acute | pt_BR |
| Subject | Protection | pt_BR |
| e-ISSN | 2076-393X | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
