Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model.
Chagas disease, caused by Trypanosoma cruzi, is endemic in southern parts of the American continent. Herein, we have tested the protective efficacy of a DNA-prime/T. rangeli-boost (TcVac4) vaccine in a dog (Canis familiaris) model. Dogs were immunized with two-doses of DNA vaccine (pcDNA3.1 encoding...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-04-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC4390229?pdf=render |
| _version_ | 1818527337760686080 |
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| author | José E Aparicio-Burgos José A Zepeda-Escobar Roberto Montes de Oca-Jimenez José G Estrada-Franco Alberto Barbabosa-Pliego Laucel Ochoa-García Ricardo Alejandre-Aguilar Nancy Rivas Giovanna Peñuelas-Rivas Margarita Val-Arreola Shivali Gupta Felix Salazar-García Nisha J Garg Juan C Vázquez-Chagoyán |
| author_facet | José E Aparicio-Burgos José A Zepeda-Escobar Roberto Montes de Oca-Jimenez José G Estrada-Franco Alberto Barbabosa-Pliego Laucel Ochoa-García Ricardo Alejandre-Aguilar Nancy Rivas Giovanna Peñuelas-Rivas Margarita Val-Arreola Shivali Gupta Felix Salazar-García Nisha J Garg Juan C Vázquez-Chagoyán |
| author_sort | José E Aparicio-Burgos |
| collection | DOAJ |
| description | Chagas disease, caused by Trypanosoma cruzi, is endemic in southern parts of the American continent. Herein, we have tested the protective efficacy of a DNA-prime/T. rangeli-boost (TcVac4) vaccine in a dog (Canis familiaris) model. Dogs were immunized with two-doses of DNA vaccine (pcDNA3.1 encoding TcG1, TcG2, and TcG4 antigens plus IL-12- and GM-CSF-encoding plasmids) followed by two doses of glutaraldehyde-inactivated T. rangeli epimastigotes (TrIE); and challenged with highly pathogenic T. cruzi (SylvioX10/4) isolate. Dogs given TrIE or empty pcDNA3.1 were used as controls. We monitored post-vaccination and post-challenge infection antibody response by an ELISA, parasitemia by blood analysis and xenodiagnosis, and heart function by electrocardiography. Post-mortem anatomic and pathologic evaluation of the heart was conducted. TcVac4 induced a strong IgG response (IgG2>IgG1) that was significantly expanded post-infection, and moved to a nearly balanced IgG2/IgG1 response in chronic phase. In comparison, dogs given TrIE or empty plasmid DNA only developed high IgG titers with IgG2 predominance in response to T. cruzi infection. Blood parasitemia, tissue parasite foci, parasite transmission to triatomines, electrocardiographic abnormalities were significantly lower in TcVac4-vaccinated dogs than was observed in dogs given TrIE or empty plasmid DNA only. Macroscopic and microscopic alterations, the hallmarks of chronic Chagas disease, were significantly decreased in the myocardium of TcVac4-vaccinated dogs. We conclude that TcVac4 induced immunity was beneficial in providing resistance to T. cruzi infection, evidenced by control of chronic pathology of the heart and preservation of cardiac function in dogs. Additionally, TcVac4 vaccination decreased the transmission of parasites from vaccinated/infected animals to triatomines. |
| first_indexed | 2024-12-11T06:34:48Z |
| format | Article |
| id | doaj.art-46dfa7ef598844e58576188c53aaa662 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-11T06:34:48Z |
| publishDate | 2015-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-46dfa7ef598844e58576188c53aaa6622022-12-22T01:17:24ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352015-04-0194e000362510.1371/journal.pntd.0003625Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model.José E Aparicio-BurgosJosé A Zepeda-EscobarRoberto Montes de Oca-JimenezJosé G Estrada-FrancoAlberto Barbabosa-PliegoLaucel Ochoa-GarcíaRicardo Alejandre-AguilarNancy RivasGiovanna Peñuelas-RivasMargarita Val-ArreolaShivali GuptaFelix Salazar-GarcíaNisha J GargJuan C Vázquez-ChagoyánChagas disease, caused by Trypanosoma cruzi, is endemic in southern parts of the American continent. Herein, we have tested the protective efficacy of a DNA-prime/T. rangeli-boost (TcVac4) vaccine in a dog (Canis familiaris) model. Dogs were immunized with two-doses of DNA vaccine (pcDNA3.1 encoding TcG1, TcG2, and TcG4 antigens plus IL-12- and GM-CSF-encoding plasmids) followed by two doses of glutaraldehyde-inactivated T. rangeli epimastigotes (TrIE); and challenged with highly pathogenic T. cruzi (SylvioX10/4) isolate. Dogs given TrIE or empty pcDNA3.1 were used as controls. We monitored post-vaccination and post-challenge infection antibody response by an ELISA, parasitemia by blood analysis and xenodiagnosis, and heart function by electrocardiography. Post-mortem anatomic and pathologic evaluation of the heart was conducted. TcVac4 induced a strong IgG response (IgG2>IgG1) that was significantly expanded post-infection, and moved to a nearly balanced IgG2/IgG1 response in chronic phase. In comparison, dogs given TrIE or empty plasmid DNA only developed high IgG titers with IgG2 predominance in response to T. cruzi infection. Blood parasitemia, tissue parasite foci, parasite transmission to triatomines, electrocardiographic abnormalities were significantly lower in TcVac4-vaccinated dogs than was observed in dogs given TrIE or empty plasmid DNA only. Macroscopic and microscopic alterations, the hallmarks of chronic Chagas disease, were significantly decreased in the myocardium of TcVac4-vaccinated dogs. We conclude that TcVac4 induced immunity was beneficial in providing resistance to T. cruzi infection, evidenced by control of chronic pathology of the heart and preservation of cardiac function in dogs. Additionally, TcVac4 vaccination decreased the transmission of parasites from vaccinated/infected animals to triatomines.http://europepmc.org/articles/PMC4390229?pdf=render |
| spellingShingle | José E Aparicio-Burgos José A Zepeda-Escobar Roberto Montes de Oca-Jimenez José G Estrada-Franco Alberto Barbabosa-Pliego Laucel Ochoa-García Ricardo Alejandre-Aguilar Nancy Rivas Giovanna Peñuelas-Rivas Margarita Val-Arreola Shivali Gupta Felix Salazar-García Nisha J Garg Juan C Vázquez-Chagoyán Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model. PLoS Neglected Tropical Diseases |
| title | Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model. |
| title_full | Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model. |
| title_fullStr | Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model. |
| title_full_unstemmed | Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model. |
| title_short | Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model. |
| title_sort | immune protection against trypanosoma cruzi induced by tcvac4 in a canine model |
| url | http://europepmc.org/articles/PMC4390229?pdf=render |
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