A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2019 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/35123 |
Resumo: | The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA. |
| id |
CRUZ_fc8d50ef3ae3469bef5f7bc574186424 |
|---|---|
| oai_identifier_str |
oai:www.arca.fiocruz.br:icict/35123 |
| network_acronym_str |
CRUZ |
| network_name_str |
Repositório Institucional da FIOCRUZ (ARCA) |
| repository_id_str |
2135 |
| spelling |
Portillo, SusanaZepeda, Brenda G.Iniguez, EvaOlivas, Janet J.Karimi, Nasim H.Moreira, Octacilio C.Marques, Alexandre F,Michael, KatjaMaldonado, Rosa A.Almeida, Igor C.2019-08-27T16:41:42Z2019-08-27T16:41:42Z2019PORTILLO, Susana et al. A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease. Vaccines, n. 13, p. 1-15, 2019.2076-393Xhttps://www.arca.fiocruz.br/handle/icict/3512310.1038/s41541-019-0107-72076-393XengMDPIGlicovacina profiláticaα-GalDoença de Chagas agudaProteçãoProphylactic α-Gal-based glycovaccineChagas DiseaseMurine acuteProtectionA prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas diseaseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleThe University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA.The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA.The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA.The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA.The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.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.The University of Texas at El Paso. Border Biomedical Research Center. Department of Chemistry and Biochemistry. El Paso, TX, USA.The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA.The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA.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.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/35123/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALOtacilioMoreira_IgorAlmeida_etal_IOC_2019.pdfOtacilioMoreira_IgorAlmeida_etal_IOC_2019.pdfapplication/pdf2423514https://www.arca.fiocruz.br/bitstream/icict/35123/2/OtacilioMoreira_IgorAlmeida_etal_IOC_2019.pdf004447667b5c80ea53e90d45e3144b82MD52TEXTOtacilioMoreira_IgorAlmeida_etal_IOC_2019.pdf.txtOtacilioMoreira_IgorAlmeida_etal_IOC_2019.pdf.txtExtracted texttext/plain100760https://www.arca.fiocruz.br/bitstream/icict/35123/3/OtacilioMoreira_IgorAlmeida_etal_IOC_2019.pdf.txt6b72330e5538437850535d6c43d90e32MD53icict/351232019-08-30 20:43:17.493oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352019-08-30T23:43:17Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease |
| title |
A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease |
| spellingShingle |
A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease Portillo, Susana Glicovacina profilática α-Gal Doença de Chagas aguda Proteção Prophylactic α-Gal-based glycovaccine Chagas Disease Murine acute Protection |
| title_short |
A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease |
| title_full |
A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease |
| title_fullStr |
A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease |
| title_full_unstemmed |
A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease |
| title_sort |
A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease |
| author |
Portillo, Susana |
| author_facet |
Portillo, Susana Zepeda, Brenda G. Iniguez, Eva Olivas, Janet J. Karimi, Nasim H. Moreira, Octacilio C. Marques, Alexandre F, Michael, Katja Maldonado, Rosa A. Almeida, Igor C. |
| author_role |
author |
| author2 |
Zepeda, Brenda G. Iniguez, Eva Olivas, Janet J. Karimi, Nasim H. Moreira, Octacilio C. Marques, Alexandre F, Michael, Katja Maldonado, Rosa A. Almeida, Igor C. |
| author2_role |
author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Portillo, Susana Zepeda, Brenda G. Iniguez, Eva Olivas, Janet J. Karimi, Nasim H. Moreira, Octacilio C. Marques, Alexandre F, Michael, Katja Maldonado, Rosa A. Almeida, Igor C. |
| dc.subject.other.pt_BR.fl_str_mv |
Glicovacina profilática α-Gal Doença de Chagas aguda Proteção |
| topic |
Glicovacina profilática α-Gal Doença de Chagas aguda Proteção Prophylactic α-Gal-based glycovaccine Chagas Disease Murine acute Protection |
| dc.subject.en.pt_BR.fl_str_mv |
Prophylactic α-Gal-based glycovaccine Chagas Disease Murine acute Protection |
| description |
The University of Texas at El Paso. Border Biomedical Research Center. Department of Biological Sciences. El Paso, El Paso, TX, USA. |
| publishDate |
2019 |
| dc.date.accessioned.fl_str_mv |
2019-08-27T16:41:42Z |
| dc.date.available.fl_str_mv |
2019-08-27T16:41:42Z |
| dc.date.issued.fl_str_mv |
2019 |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.citation.fl_str_mv |
PORTILLO, Susana et al. A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease. Vaccines, n. 13, p. 1-15, 2019. |
| dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/35123 |
| dc.identifier.issn.pt_BR.fl_str_mv |
2076-393X |
| dc.identifier.doi.pt_BR.fl_str_mv |
10.1038/s41541-019-0107-7 |
| dc.identifier.eissn.none.fl_str_mv |
2076-393X |
| identifier_str_mv |
PORTILLO, Susana et al. A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease. Vaccines, n. 13, p. 1-15, 2019. 2076-393X 10.1038/s41541-019-0107-7 |
| url |
https://www.arca.fiocruz.br/handle/icict/35123 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
MDPI |
| publisher.none.fl_str_mv |
MDPI |
| dc.source.none.fl_str_mv |
reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
| instname_str |
Fundação Oswaldo Cruz (FIOCRUZ) |
| instacron_str |
FIOCRUZ |
| institution |
FIOCRUZ |
| reponame_str |
Repositório Institucional da FIOCRUZ (ARCA) |
| collection |
Repositório Institucional da FIOCRUZ (ARCA) |
| bitstream.url.fl_str_mv |
https://www.arca.fiocruz.br/bitstream/icict/35123/1/license.txt https://www.arca.fiocruz.br/bitstream/icict/35123/2/OtacilioMoreira_IgorAlmeida_etal_IOC_2019.pdf https://www.arca.fiocruz.br/bitstream/icict/35123/3/OtacilioMoreira_IgorAlmeida_etal_IOC_2019.pdf.txt |
| bitstream.checksum.fl_str_mv |
5a560609d32a3863062d77ff32785d58 004447667b5c80ea53e90d45e3144b82 6b72330e5538437850535d6c43d90e32 |
| bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
| repository.name.fl_str_mv |
Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ) |
| repository.mail.fl_str_mv |
repositorio.arca@fiocruz.br |
| _version_ |
1822791520468598784 |