α-Gal immunization positively impacts Trypanosoma cruzi colonization of heart tissue in a mouse model

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...

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Veröffentlicht in:PLoS neglected tropical diseases 2021-07, Vol.15 (7), p.e0009613-e0009613
Hauptverfasser: Rodrigues da Cunha, Gisele Macêdo, Azevedo, Maíra Araújo, Nogueira, Denise Silva, Clímaco, Marianna de Carvalho, Valencia Ayala, Edward, Jimenez Chunga, Juan Atilio, La Valle, Raul Jesus Ynocente, da Cunha Galvão, Lucia Maria, Chiari, Egler, Brito, Carlos Ramon Nascimento, Soares, Rodrigo Pedro, Nogueira, Paula Monalisa, Fujiwara, Ricardo Toshio, Gazzinelli, Ricardo, Hincapie, Robert, Chaves, Carlos-Sanhueza, Oliveira, Fabricio Marcus Silva, Finn, M. G., Marques, Alexandre Ferreira
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container_issue 7
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container_title PLoS neglected tropical diseases
container_volume 15
creator Rodrigues da Cunha, Gisele Macêdo
Azevedo, Maíra Araújo
Nogueira, Denise Silva
Clímaco, Marianna de Carvalho
Valencia Ayala, Edward
Jimenez Chunga, Juan Atilio
La Valle, Raul Jesus Ynocente
da Cunha Galvão, Lucia Maria
Chiari, Egler
Brito, Carlos Ramon Nascimento
Soares, Rodrigo Pedro
Nogueira, Paula Monalisa
Fujiwara, Ricardo Toshio
Gazzinelli, Ricardo
Hincapie, Robert
Chaves, Carlos-Sanhueza
Oliveira, Fabricio Marcus Silva
Finn, M. G.
Marques, Alexandre Ferreira
description 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 α-Gal trisaccharide (Qβ-αGal) induced several beneficial effects concerning acute and chronic T . cruzi infection in α1,3-galactosyltransferase knockout mice. Approximately 60% of these animals were protected from initial infection with high parasite loads. Vaccinated animals also produced high anti-αGal IgG antibody titers, improved IFN-γ 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.
doi_str_mv 10.1371/journal.pntd.0009613
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G.</au><au>Marques, Alexandre Ferreira</au><au>Lopes, Ulisses Gazos</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>α-Gal immunization positively impacts Trypanosoma cruzi colonization of heart tissue in a mouse model</atitle><jtitle>PLoS neglected tropical diseases</jtitle><date>2021-07-01</date><risdate>2021</risdate><volume>15</volume><issue>7</issue><spage>e0009613</spage><epage>e0009613</epage><pages>e0009613-e0009613</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>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 α-Gal trisaccharide (Qβ-αGal) induced several beneficial effects concerning acute and chronic T . cruzi infection in α1,3-galactosyltransferase knockout mice. Approximately 60% of these animals were protected from initial infection with high parasite loads. Vaccinated animals also produced high anti-αGal IgG antibody titers, improved IFN-γ 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.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>34314435</pmid><doi>10.1371/journal.pntd.0009613</doi><orcidid>https://orcid.org/0000-0001-8247-3108</orcidid><orcidid>https://orcid.org/0000-0001-7358-4543</orcidid><orcidid>https://orcid.org/0000-0001-8822-6036</orcidid><orcidid>https://orcid.org/0000-0001-6201-6313</orcidid><orcidid>https://orcid.org/0000-0001-8627-3082</orcidid><orcidid>https://orcid.org/0000-0003-4882-5215</orcidid><orcidid>https://orcid.org/0000-0002-7966-3629</orcidid><orcidid>https://orcid.org/0000-0003-4091-8783</orcidid><orcidid>https://orcid.org/0000-0003-1670-7791</orcidid><orcidid>https://orcid.org/0000-0001-9416-3465</orcidid><orcidid>https://orcid.org/0000-0002-0128-3028</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1935-2735
ispartof PLoS neglected tropical diseases, 2021-07, Vol.15 (7), p.e0009613-e0009613
issn 1935-2735
1935-2727
1935-2735
language eng
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source DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; Public Library of Science (PLoS); PubMed Central
subjects Animal tissues
Animals
Antibodies
Biology and Life Sciences
Cardiomyocytes
Cardiomyopathy
Chagas disease
Chronic infection
Colonization
Cytokines
Disease control
Experiments
Heart
IgG antibody
Immunization
Immunogenicity
Immunoglobulin G
Infections
Inflammation
Interleukin 12
Medicine and Health Sciences
Microbiological strains
Nests
Oligosaccharides
Parasitemia
Parasites
Parasitic diseases
Protected animals
Protozoa
Standard deviation
Strain
Survival
Tissue
Tropical diseases
Trypanosoma cruzi
Vaccines
Vector-borne diseases
Viral infections
Virus-like particles
Viruses
γ-Interferon
title α-Gal immunization positively impacts Trypanosoma cruzi colonization of heart tissue in a mouse model
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