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 |
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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 |
format | Article |
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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.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0009613</identifier><identifier>PMID: 34314435</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>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</subject><ispartof>PLoS neglected tropical diseases, 2021-07, Vol.15 (7), p.e0009613-e0009613</ispartof><rights>2021 Rodrigues da Cunha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Rodrigues da Cunha et al 2021 Rodrigues da Cunha et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-7f513b9ab0a6145ff010c5604d3063dabf770fe1929bd02b1243114c0c987faf3</citedby><cites>FETCH-LOGICAL-c503t-7f513b9ab0a6145ff010c5604d3063dabf770fe1929bd02b1243114c0c987faf3</cites><orcidid>0000-0001-8247-3108 ; 0000-0001-7358-4543 ; 0000-0001-8822-6036 ; 0000-0001-6201-6313 ; 0000-0001-8627-3082 ; 0000-0003-4882-5215 ; 0000-0002-7966-3629 ; 0000-0003-4091-8783 ; 0000-0003-1670-7791 ; 0000-0001-9416-3465 ; 0000-0002-0128-3028</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345864/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345864/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids></links><search><contributor>Lopes, Ulisses Gazos</contributor><creatorcontrib>Rodrigues da Cunha, Gisele Macêdo</creatorcontrib><creatorcontrib>Azevedo, Maíra Araújo</creatorcontrib><creatorcontrib>Nogueira, Denise Silva</creatorcontrib><creatorcontrib>Clímaco, Marianna de Carvalho</creatorcontrib><creatorcontrib>Valencia Ayala, Edward</creatorcontrib><creatorcontrib>Jimenez Chunga, Juan Atilio</creatorcontrib><creatorcontrib>La Valle, Raul Jesus Ynocente</creatorcontrib><creatorcontrib>da Cunha Galvão, Lucia Maria</creatorcontrib><creatorcontrib>Chiari, Egler</creatorcontrib><creatorcontrib>Brito, Carlos Ramon Nascimento</creatorcontrib><creatorcontrib>Soares, Rodrigo Pedro</creatorcontrib><creatorcontrib>Nogueira, Paula Monalisa</creatorcontrib><creatorcontrib>Fujiwara, Ricardo Toshio</creatorcontrib><creatorcontrib>Gazzinelli, Ricardo</creatorcontrib><creatorcontrib>Hincapie, Robert</creatorcontrib><creatorcontrib>Chaves, Carlos-Sanhueza</creatorcontrib><creatorcontrib>Oliveira, Fabricio Marcus Silva</creatorcontrib><creatorcontrib>Finn, M. G.</creatorcontrib><creatorcontrib>Marques, Alexandre Ferreira</creatorcontrib><title>α-Gal immunization positively impacts Trypanosoma cruzi colonization of heart tissue in a mouse model</title><title>PLoS neglected tropical diseases</title><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.</description><subject>Animal tissues</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Biology and Life Sciences</subject><subject>Cardiomyocytes</subject><subject>Cardiomyopathy</subject><subject>Chagas disease</subject><subject>Chronic infection</subject><subject>Colonization</subject><subject>Cytokines</subject><subject>Disease control</subject><subject>Experiments</subject><subject>Heart</subject><subject>IgG antibody</subject><subject>Immunization</subject><subject>Immunogenicity</subject><subject>Immunoglobulin G</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Interleukin 12</subject><subject>Medicine and Health Sciences</subject><subject>Microbiological strains</subject><subject>Nests</subject><subject>Oligosaccharides</subject><subject>Parasitemia</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Protected animals</subject><subject>Protozoa</subject><subject>Standard deviation</subject><subject>Strain</subject><subject>Survival</subject><subject>Tissue</subject><subject>Tropical diseases</subject><subject>Trypanosoma cruzi</subject><subject>Vaccines</subject><subject>Vector-borne diseases</subject><subject>Viral infections</subject><subject>Virus-like particles</subject><subject>Viruses</subject><subject>γ-Interferon</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNptUstq3TAQNaWhSZP8QaGCbrrxrcaS_NgUSmjTQKCbZC3GspToIluuJAdu_qo_0m-q0uuGpGSjETNnzswZTlG8A7oB1sCnrV_ChG4zT2nYUEq7Gtir4gg6JsqqYeL1k_9h8TbGLaWiEy28KQ4ZZ8A5E0eF-f2rPEdH7Dguk73HZP1EZh9tsnfa7XJ-RpUiuQq7GScf_YhEheXeEuWdf-zwhtxqDIkkG-OiiZ0IktEvUed30O6kODDooj5d43Fx_e3r1dn38vLH-cXZl8tSCcpS2RgBrO-wp1gDF8ZQoErUlA-M1mzA3jQNNRq6qusHWvVQZSHAFVVd2xg07Lh4v-ednY9yPVGUlajzLTrGISMu9ojB41bOwY4YdtKjlX8TPtzIrMMqp6XQIKCqW1RDz-vB9KZqsc3jWsBaV23m-rxOW_pRD0pPKaB7Rvq8MtlbeePvZMu4aGueCT6uBMH_XHRMcrRRaedw0vl4eW8hugZyyNAP_0FfVsf3KBV8jEGbx2WAygfb_OuSD7aRq23YH70CuUg</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Rodrigues da Cunha, Gisele Macêdo</creator><creator>Azevedo, Maíra Araújo</creator><creator>Nogueira, Denise Silva</creator><creator>Clímaco, Marianna de Carvalho</creator><creator>Valencia Ayala, Edward</creator><creator>Jimenez Chunga, Juan Atilio</creator><creator>La Valle, Raul Jesus Ynocente</creator><creator>da Cunha Galvão, Lucia Maria</creator><creator>Chiari, Egler</creator><creator>Brito, Carlos Ramon Nascimento</creator><creator>Soares, Rodrigo Pedro</creator><creator>Nogueira, Paula Monalisa</creator><creator>Fujiwara, Ricardo Toshio</creator><creator>Gazzinelli, Ricardo</creator><creator>Hincapie, Robert</creator><creator>Chaves, Carlos-Sanhueza</creator><creator>Oliveira, Fabricio Marcus Silva</creator><creator>Finn, M. 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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 |
recordid | cdi_plos_journals_2561939341 |
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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