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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Autor principal: Levitus, G.
Otros Autores: Grippo, V., Labovsky, V., Ghio, S., Hontebeyrie, M., Levin, M.J
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: Elsevier Masson SAS 2003
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100 1 |a Levitus, G. 
245 1 0 |a DNA immunization with the ribosomal P2β gene of Trypanosoma cruzi fails to induce pathogenic antibodies 
260 |b Elsevier Masson SAS  |c 2003 
270 1 0 |m Levin, M.J.; Lab. Biol. Molec. Enfermedad Chagas, Inst. Invest. Ing. Genet. Biol. M., Vuelta de Obligado 2490, Buenos Aires, 1428, Argentina; email: mlevin@dna.uba.ar 
506 |2 openaire  |e Política editorial 
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504 |a Sepulveda, P., Liegeard, P., Wallukat, G., Levin, M.J., Hontebeyrie, M., Modulation of cardiocyte functional activity by antibodies against Trypanosoma cruzi ribosomal P2 protein C-terminus (2000) Infect. Immun., 68, pp. 5114-5119 
504 |a Gurunathan, S., Wu, C.Y., Freidag, B.L., Seder, R.A., DNA vaccines: A key for inducing long-term cellular immunity (2000) Curr. Opin. Immunol., 12, pp. 442-447 
504 |a Mahler, E., Sepulveda, P., Jeannequin, O., Liegeard, P., Gounon, P., Wallukat, G., Eftekhari, P., Hontebeyrie, M., A monoclonal antibody against the immunodominant epitope of the ribosomal P2β protein of Trypanosoma cruzi interacts with the human β1-adrenergic receptor (2001) Eur. J. Immunol., 31, pp. 2210-2216 
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504 |a Schijman, A., Dusetti, N.J., Vázquez, M.P., Lafon, S., Levy-Yeyati, P., Levin, M.J., Nucleotide cDNA and complete deduced amino acid sequence of a Trypanosoma cruzi ribosomal P protein (P-JL5) (1990) Nucleic Acids Res., 18, p. 3399 
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504 |a Sin, J.I., Kim, J.J., Ugen, K.E., Ciccarelli, R.B., Higgins, T.J., Weiner, D.B., Enhancement of protective humoral (Th2) and cell-mediated (Th1) immune responses against herpes simplex virus-2 through co-delivery of granulocyte-macrophage colony-stimulating factor expression cassettes (1998) Eur. J. Immunol., 28, pp. 3530-3540 
504 |a Weiss, W.R., Ishii, K.J., Hedstrom, R.C., Sedegah, M., Ichino, M., Barnhart, K., Klinman, D.M., Hoffman, S.L., A plasmid encoding murine granulocyte-macrophage colony-stimulating factor increases protection conferred by a malaria DNA vaccine (1998) J. Immunol., 161, pp. 2325-2332 
504 |a Leclerc, C., Deriaud, E., Rojas, M., Whalen, R.G., The preferential induction of a Th1 immune response by DNA-based immunization is mediated by the immunostimulatory effect of plasmid DNA (1997) Cell Immunol., 179, pp. 97-106 
504 |a Peng, H.J., Su, S.N., Chang, Z.N., Chao, P.L., Kuo, S.W., Tsai, L.C., Induction of specific Th1 responses and suppression of IgE antibody formation by vaccination with plasmid DNA encoding der f 11 (2002) Vaccine, 20, pp. 1761-1768 
504 |a Sharma, A.K., Khuller, G.K., DNA vaccines: Future strategies and relevance to intracellular pathogens (2001) Immunol. Cell Biol., 79, pp. 537-546 
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504 |a Minoprio, P., Burlen, O., Pereira, P., Guilbert, B., Andrade, L., Hontebeyrie-Joskowicz, M., Coutinho, A., Most B cells in acute Trypanosoma cruzi infection lack parasite specificity (1988) Scand. J. Immunol., 28, pp. 553-561 
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504 |a Garcia, F., Sepulveda, P., Liegeard, P., Gregoire, J., Hermann, E., Lemonnier, F., Langlade-Demoyen, P., Lone, Y.C., Identification of HLA-A*0201-restricted cytotoxic T-cell epitopes of Trypanosoma cruzi TcP2β protein in HLA-transgenic mice and patients (2003) Microbes Infect., 5, pp. 351-359 
520 3 |a 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.  |l eng 
536 |a Detalles de la financiación: Howard Hughes Medical Institute 
536 |a Detalles de la financiación: Universidad de Buenos Aires 
536 |a Detalles de la financiación: Fondo para la Investigación Científica y Tecnológica, BID 1201/OC-AR 05-06802 
536 |a Detalles de la financiación: We are grateful to Evelina Mahler (INGEBI, Buenos Aires, Argentina) for helpful discussion. We also thank Dr. Mauricio Rodrigues (Escola Paulista de Medicina, São Paulo, Brazil) for kindly providing the pcDNA3/GM-CSF plasmid and Dr. Reza Mobini (Sahlgrenska University Hospital, Gothenburg, Sweden) for providing MAbM16. This work was supported by grants from (i) the World Health Organization/Special Program for Research and Training in Tropical Diseases, Universidad de Buenos Aires, (ii) FONCYT BID 1201/OC-AR 05-06802, and (iii) INSERM-CONICET Joint Research Program (Project Hontebeyrie/Levin). In addition, the work of Dr. Mariano J. Levin is partially supported by an International Research Scholar grant from the Howard Hughes Medical Institute, Chevy Chase, MD, USA. 
593 |a Lab. Biol. Molec. Enfermedad Chagas, Inst. Invest. Ing. Genet. Biol. M., Vuelta de Obligado 2490, Buenos Aires, 1428, Argentina 
593 |a Depto. Fisiol. y Biol. Molec. y Cel., Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina 
593 |a U. Repliement Modelisation Proteines, Dept. de Biol. Structurale et Chimie, Institut Pasteur, 28, rue du Dr Roux, 75724 Paris Cedex 15, France 
690 1 0 |a DNA IMMUNIZATION 
690 1 0 |a RIBOSOMAL P2 PROTEIN 
690 1 0 |a TRYPANOSOMA CRUZI 
690 1 0 |a CYCLIC AMP 
690 1 0 |a DNA VACCINE 
690 1 0 |a EPITOPE 
690 1 0 |a IMMUNOGLOBULIN G ANTIBODY 
690 1 0 |a PROTOZOAL PROTEIN 
690 1 0 |a PROTOZOON ANTIBODY 
690 1 0 |a RECOMBINANT PROTEIN 
690 1 0 |a RIBOSOME PROTEIN 
690 1 0 |a ANIMAL CELL 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ANIMAL MODEL 
690 1 0 |a ANTIBODY DETECTION 
690 1 0 |a ANTIBODY PRODUCTION 
690 1 0 |a ANTIBODY SPECIFICITY 
690 1 0 |a ARTICLE 
690 1 0 |a CELL STRAIN COS7 
690 1 0 |a CHAGAS DISEASE 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a DRUG EFFECT 
690 1 0 |a ELECTROCARDIOGRAPHY 
690 1 0 |a FEMALE 
690 1 0 |a GENETIC TRANSFECTION 
690 1 0 |a HUMAN 
690 1 0 |a HUMORAL IMMUNITY 
690 1 0 |a IMMUNIZATION 
690 1 0 |a MOUSE 
690 1 0 |a NONHUMAN 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a TRYPANOSOMA CRUZI 
690 1 0 |a TRYPANOSOMIASIS 
690 1 0 |a TRYPANOSOMA 
690 1 0 |a TRYPANOSOMA CRUZI 
700 1 |a Grippo, V. 
700 1 |a Labovsky, V. 
700 1 |a Ghio, S. 
700 1 |a Hontebeyrie, M. 
700 1 |a Levin, M.J. 
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