DNA immunization with the ribosomal P2β gene of Trypanosoma cruzi fails to induce pathogenic antibodies
Patients with chronic Chagas' heart disease (cChHD) develop a strong IgG response against the C-terminal region of the Trypanosoma cruzi ribosomal P2β protein (TcP2β). These antibodies have been shown to exert an in vitro chronotropic effect on cardiocytes through stimulation of the β1-adrenerg...
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2003
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_12864579_v5_n15_p1381_Levitus http://hdl.handle.net/20.500.12110/paper_12864579_v5_n15_p1381_Levitus |
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paper:paper_12864579_v5_n15_p1381_Levitus2023-06-08T16:10:13Z DNA immunization with the ribosomal P2β gene of Trypanosoma cruzi fails to induce pathogenic antibodies Levitus, Gabriela Laura Grippo, Vanina Labovsky, Vivian Ghio, Sergio Claudio DNA immunization Ribosomal P2 protein Trypanosoma cruzi cyclic AMP DNA vaccine epitope immunoglobulin G antibody protozoal protein protozoon antibody recombinant protein ribosome protein animal cell animal experiment animal model antibody detection antibody production antibody specificity article cell strain COS7 Chagas disease controlled study drug effect electrocardiography female genetic transfection human humoral immunity immunization mouse nonhuman priority journal Trypanosoma cruzi trypanosomiasis Trypanosoma Trypanosoma cruzi Patients with chronic Chagas' heart disease (cChHD) develop a strong IgG response against the C-terminal region of the Trypanosoma cruzi ribosomal P2β protein (TcP2β). These antibodies have been shown to exert an in vitro chronotropic effect on cardiocytes through stimulation of the β1-adrenergic receptor (β1-AR). Moreover, the presence of antibodies recognizing the TcP2β C-terminus was associated with cardiac alterations in mice immunized with the corresponding recombinant protein. Here, we demonstrate that DNA immunization could be used to modulate the specificity of the anti-TcP2β humoral response in order to avoid the production of pathogenic antibodies. After DNA injection, we detected IgG antibodies that were directed only to internal epitopes of the TcP2β molecule and that did not exert anti-β1-AR functional activity, measured as an increase in intracellular cAMP levels of transfected COS-7 cells. Accordingly, DNA-immunized mice did not present electrocardiographic alterations. These data demonstrate that anti-TcP2β antibodies elicited by DNA immunization are completely different in their specificity and functional activity from those produced during T. cruzi infection. © 2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. Fil:Levitus, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Grippo, V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Labovsky, V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ghio, S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2003 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_12864579_v5_n15_p1381_Levitus http://hdl.handle.net/20.500.12110/paper_12864579_v5_n15_p1381_Levitus |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
DNA immunization Ribosomal P2 protein Trypanosoma cruzi cyclic AMP DNA vaccine epitope immunoglobulin G antibody protozoal protein protozoon antibody recombinant protein ribosome protein animal cell animal experiment animal model antibody detection antibody production antibody specificity article cell strain COS7 Chagas disease controlled study drug effect electrocardiography female genetic transfection human humoral immunity immunization mouse nonhuman priority journal Trypanosoma cruzi trypanosomiasis Trypanosoma Trypanosoma cruzi |
| spellingShingle |
DNA immunization Ribosomal P2 protein Trypanosoma cruzi cyclic AMP DNA vaccine epitope immunoglobulin G antibody protozoal protein protozoon antibody recombinant protein ribosome protein animal cell animal experiment animal model antibody detection antibody production antibody specificity article cell strain COS7 Chagas disease controlled study drug effect electrocardiography female genetic transfection human humoral immunity immunization mouse nonhuman priority journal Trypanosoma cruzi trypanosomiasis Trypanosoma Trypanosoma cruzi Levitus, Gabriela Laura Grippo, Vanina Labovsky, Vivian Ghio, Sergio Claudio DNA immunization with the ribosomal P2β gene of Trypanosoma cruzi fails to induce pathogenic antibodies |
| topic_facet |
DNA immunization Ribosomal P2 protein Trypanosoma cruzi cyclic AMP DNA vaccine epitope immunoglobulin G antibody protozoal protein protozoon antibody recombinant protein ribosome protein animal cell animal experiment animal model antibody detection antibody production antibody specificity article cell strain COS7 Chagas disease controlled study drug effect electrocardiography female genetic transfection human humoral immunity immunization mouse nonhuman priority journal Trypanosoma cruzi trypanosomiasis Trypanosoma Trypanosoma cruzi |
| description |
Patients with chronic Chagas' heart disease (cChHD) develop a strong IgG response against the C-terminal region of the Trypanosoma cruzi ribosomal P2β protein (TcP2β). These antibodies have been shown to exert an in vitro chronotropic effect on cardiocytes through stimulation of the β1-adrenergic receptor (β1-AR). Moreover, the presence of antibodies recognizing the TcP2β C-terminus was associated with cardiac alterations in mice immunized with the corresponding recombinant protein. Here, we demonstrate that DNA immunization could be used to modulate the specificity of the anti-TcP2β humoral response in order to avoid the production of pathogenic antibodies. After DNA injection, we detected IgG antibodies that were directed only to internal epitopes of the TcP2β molecule and that did not exert anti-β1-AR functional activity, measured as an increase in intracellular cAMP levels of transfected COS-7 cells. Accordingly, DNA-immunized mice did not present electrocardiographic alterations. These data demonstrate that anti-TcP2β antibodies elicited by DNA immunization are completely different in their specificity and functional activity from those produced during T. cruzi infection. © 2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. |
| author |
Levitus, Gabriela Laura Grippo, Vanina Labovsky, Vivian Ghio, Sergio Claudio |
| author_facet |
Levitus, Gabriela Laura Grippo, Vanina Labovsky, Vivian Ghio, Sergio Claudio |
| author_sort |
Levitus, Gabriela Laura |
| title |
DNA immunization with the ribosomal P2β gene of Trypanosoma cruzi fails to induce pathogenic antibodies |
| title_short |
DNA immunization with the ribosomal P2β gene of Trypanosoma cruzi fails to induce pathogenic antibodies |
| title_full |
DNA immunization with the ribosomal P2β gene of Trypanosoma cruzi fails to induce pathogenic antibodies |
| title_fullStr |
DNA immunization with the ribosomal P2β gene of Trypanosoma cruzi fails to induce pathogenic antibodies |
| title_full_unstemmed |
DNA immunization with the ribosomal P2β gene of Trypanosoma cruzi fails to induce pathogenic antibodies |
| title_sort |
dna immunization with the ribosomal p2β gene of trypanosoma cruzi fails to induce pathogenic antibodies |
| publishDate |
2003 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_12864579_v5_n15_p1381_Levitus http://hdl.handle.net/20.500.12110/paper_12864579_v5_n15_p1381_Levitus |
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| _version_ |
1768543670567436288 |