Recombinant mycobacterium bovis bcg is a promising platform to develop vaccines against Trypansoma Cruzi infections

Autores
Bontempi, Iván; Díaz, Genaro Francisco; Leal ,Karen; Prochetto, Estefanía Soledad; Borsuk, Sibele; Dellagostin, Odir; Marcipar, Iván Sergio
Año de publicación
2020
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Chagas disease is caused by human infection with the parasite Trypanosoma cruzi, affecting more than 7 million people worldwide, and there is not yet a vaccine available to control this protozoan infection. BCG vaccine has been extensively used as antigens delivery platform to reach immunity against many infection models, however it has not been described in T. cruzi infection. In the present study, we evaluated recombinant BCG (rBCG) expressing three T. cruzi antigens: two derived from Trans-sialidase (NT-TS, CT-TS) and one from Cruzipain (CZf). Each antigen was cloned into two different vectors able to replicate in Mycobacterium bovis and each construction was transformed in the BCG Pasteur strain. We immunized groups of BALB/c mice with the six rBCGs and controls with BCG Pasteur and PBS. Thirty days after the last immunization animals were challenged with 1,000 T. cruzi. The immunoprotective potential of rBCGs strains against T. cruzi was evaluated and a significant survival rates after challenge were observed only in NT-TS group (p<0.05). Histological analysis of NT-TS mice during the chronic phase of the infection revealed a decrease of heart inflammatory infiltrates and fibrosis (p<0.05; NT-TS vs control group). Cellular response was evaluated after mice immunizations with NT-TS, BCG Pasteur or PBS by stimulating splenocytes in vitro with recombinant antigens. CD4+ T cells of NT-TS immunized mice increased: proliferative capacity (Ki67+) and cytokine intracellular production (IFN-y and IL-17) as compared with controls groups (p<0.05). Furthermore CD8+/CD107+ T cells exhibited a high IFN-y; production compared with control groups (p<0.05). We conclude that the immunization with NT-TS expressed in rBCG conferred a very significant protection that was correlated with the activation of CD4+ T cells corresponding to both a TH1 and TH17 profile. More studies aimed to increase antigen expression could allow to improve the response obtained with this vaccine.
Fil: Bontempi, Iván. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Díaz, Genaro Francisco. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Leal ,Karen. Universidade Federal de Pelotas; Brasil
Fil: Prochetto, Estefanía Soledad. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Borsuk, Sibele. Universidade Federal de Pelotas; Brasil
Fil: Dellagostin, Odir. Universidade Federal de Pelotas; Brasil
Fil: Marcipar, Iván Sergio. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Investigación Clínica
Materia
T.CRUZI
BCG
VACCINE
TRANSIALIDASE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/286755
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Recombinant mycobacterium bovis bcg is a promising platform to develop vaccines against Trypansoma Cruzi infectionsBontempi, IvánDíaz, Genaro FranciscoLeal ,KarenProchetto, Estefanía SoledadBorsuk, SibeleDellagostin, OdirMarcipar, Iván SergioT.CRUZIBCGVACCINETRANSIALIDASEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Chagas disease is caused by human infection with the parasite Trypanosoma cruzi, affecting more than 7 million people worldwide, and there is not yet a vaccine available to control this protozoan infection. BCG vaccine has been extensively used as antigens delivery platform to reach immunity against many infection models, however it has not been described in T. cruzi infection. In the present study, we evaluated recombinant BCG (rBCG) expressing three T. cruzi antigens: two derived from Trans-sialidase (NT-TS, CT-TS) and one from Cruzipain (CZf). Each antigen was cloned into two different vectors able to replicate in Mycobacterium bovis and each construction was transformed in the BCG Pasteur strain. We immunized groups of BALB/c mice with the six rBCGs and controls with BCG Pasteur and PBS. Thirty days after the last immunization animals were challenged with 1,000 T. cruzi. The immunoprotective potential of rBCGs strains against T. cruzi was evaluated and a significant survival rates after challenge were observed only in NT-TS group (p<0.05). Histological analysis of NT-TS mice during the chronic phase of the infection revealed a decrease of heart inflammatory infiltrates and fibrosis (p<0.05; NT-TS vs control group). Cellular response was evaluated after mice immunizations with NT-TS, BCG Pasteur or PBS by stimulating splenocytes in vitro with recombinant antigens. CD4+ T cells of NT-TS immunized mice increased: proliferative capacity (Ki67+) and cytokine intracellular production (IFN-y and IL-17) as compared with controls groups (p<0.05). Furthermore CD8+/CD107+ T cells exhibited a high IFN-y; production compared with control groups (p<0.05). We conclude that the immunization with NT-TS expressed in rBCG conferred a very significant protection that was correlated with the activation of CD4+ T cells corresponding to both a TH1 and TH17 profile. More studies aimed to increase antigen expression could allow to improve the response obtained with this vaccine.Fil: Bontempi, Iván. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Díaz, Genaro Francisco. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Leal ,Karen. Universidade Federal de Pelotas; BrasilFil: Prochetto, Estefanía Soledad. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Borsuk, Sibele. Universidade Federal de Pelotas; BrasilFil: Dellagostin, Odir. Universidade Federal de Pelotas; BrasilFil: Marcipar, Iván Sergio. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaLXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PlataArgentinaSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioAsociación Argentina de Farmacología ExperimentalSociedad Argentina de Investigación ClínicaFundación Revista Medicina2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/286755Recombinant mycobacterium bovis bcg is a promising platform to develop vaccines against Trypansoma Cruzi infections; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 232-2320025-7680CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol79-19/s4/vol79_s4.pdfInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-06-17T09:44:14Zoai:ri.conicet.gov.ar:11336/286755instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-06-17 09:44:14.313CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Recombinant mycobacterium bovis bcg is a promising platform to develop vaccines against Trypansoma Cruzi infections
title Recombinant mycobacterium bovis bcg is a promising platform to develop vaccines against Trypansoma Cruzi infections
spellingShingle Recombinant mycobacterium bovis bcg is a promising platform to develop vaccines against Trypansoma Cruzi infections
Bontempi, Iván
T.CRUZI
BCG
VACCINE
TRANSIALIDASE
title_short Recombinant mycobacterium bovis bcg is a promising platform to develop vaccines against Trypansoma Cruzi infections
title_full Recombinant mycobacterium bovis bcg is a promising platform to develop vaccines against Trypansoma Cruzi infections
title_fullStr Recombinant mycobacterium bovis bcg is a promising platform to develop vaccines against Trypansoma Cruzi infections
title_full_unstemmed Recombinant mycobacterium bovis bcg is a promising platform to develop vaccines against Trypansoma Cruzi infections
title_sort Recombinant mycobacterium bovis bcg is a promising platform to develop vaccines against Trypansoma Cruzi infections
dc.creator.none.fl_str_mv Bontempi, Iván
Díaz, Genaro Francisco
Leal ,Karen
Prochetto, Estefanía Soledad
Borsuk, Sibele
Dellagostin, Odir
Marcipar, Iván Sergio
author Bontempi, Iván
author_facet Bontempi, Iván
Díaz, Genaro Francisco
Leal ,Karen
Prochetto, Estefanía Soledad
Borsuk, Sibele
Dellagostin, Odir
Marcipar, Iván Sergio
author_role author
author2 Díaz, Genaro Francisco
Leal ,Karen
Prochetto, Estefanía Soledad
Borsuk, Sibele
Dellagostin, Odir
Marcipar, Iván Sergio
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv T.CRUZI
BCG
VACCINE
TRANSIALIDASE
topic T.CRUZI
BCG
VACCINE
TRANSIALIDASE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chagas disease is caused by human infection with the parasite Trypanosoma cruzi, affecting more than 7 million people worldwide, and there is not yet a vaccine available to control this protozoan infection. BCG vaccine has been extensively used as antigens delivery platform to reach immunity against many infection models, however it has not been described in T. cruzi infection. In the present study, we evaluated recombinant BCG (rBCG) expressing three T. cruzi antigens: two derived from Trans-sialidase (NT-TS, CT-TS) and one from Cruzipain (CZf). Each antigen was cloned into two different vectors able to replicate in Mycobacterium bovis and each construction was transformed in the BCG Pasteur strain. We immunized groups of BALB/c mice with the six rBCGs and controls with BCG Pasteur and PBS. Thirty days after the last immunization animals were challenged with 1,000 T. cruzi. The immunoprotective potential of rBCGs strains against T. cruzi was evaluated and a significant survival rates after challenge were observed only in NT-TS group (p<0.05). Histological analysis of NT-TS mice during the chronic phase of the infection revealed a decrease of heart inflammatory infiltrates and fibrosis (p<0.05; NT-TS vs control group). Cellular response was evaluated after mice immunizations with NT-TS, BCG Pasteur or PBS by stimulating splenocytes in vitro with recombinant antigens. CD4+ T cells of NT-TS immunized mice increased: proliferative capacity (Ki67+) and cytokine intracellular production (IFN-y and IL-17) as compared with controls groups (p<0.05). Furthermore CD8+/CD107+ T cells exhibited a high IFN-y; production compared with control groups (p<0.05). We conclude that the immunization with NT-TS expressed in rBCG conferred a very significant protection that was correlated with the activation of CD4+ T cells corresponding to both a TH1 and TH17 profile. More studies aimed to increase antigen expression could allow to improve the response obtained with this vaccine.
Fil: Bontempi, Iván. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Díaz, Genaro Francisco. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Leal ,Karen. Universidade Federal de Pelotas; Brasil
Fil: Prochetto, Estefanía Soledad. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Borsuk, Sibele. Universidade Federal de Pelotas; Brasil
Fil: Dellagostin, Odir. Universidade Federal de Pelotas; Brasil
Fil: Marcipar, Iván Sergio. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Investigación Clínica
description Chagas disease is caused by human infection with the parasite Trypanosoma cruzi, affecting more than 7 million people worldwide, and there is not yet a vaccine available to control this protozoan infection. BCG vaccine has been extensively used as antigens delivery platform to reach immunity against many infection models, however it has not been described in T. cruzi infection. In the present study, we evaluated recombinant BCG (rBCG) expressing three T. cruzi antigens: two derived from Trans-sialidase (NT-TS, CT-TS) and one from Cruzipain (CZf). Each antigen was cloned into two different vectors able to replicate in Mycobacterium bovis and each construction was transformed in the BCG Pasteur strain. We immunized groups of BALB/c mice with the six rBCGs and controls with BCG Pasteur and PBS. Thirty days after the last immunization animals were challenged with 1,000 T. cruzi. The immunoprotective potential of rBCGs strains against T. cruzi was evaluated and a significant survival rates after challenge were observed only in NT-TS group (p<0.05). Histological analysis of NT-TS mice during the chronic phase of the infection revealed a decrease of heart inflammatory infiltrates and fibrosis (p<0.05; NT-TS vs control group). Cellular response was evaluated after mice immunizations with NT-TS, BCG Pasteur or PBS by stimulating splenocytes in vitro with recombinant antigens. CD4+ T cells of NT-TS immunized mice increased: proliferative capacity (Ki67+) and cytokine intracellular production (IFN-y and IL-17) as compared with controls groups (p<0.05). Furthermore CD8+/CD107+ T cells exhibited a high IFN-y; production compared with control groups (p<0.05). We conclude that the immunization with NT-TS expressed in rBCG conferred a very significant protection that was correlated with the activation of CD4+ T cells corresponding to both a TH1 and TH17 profile. More studies aimed to increase antigen expression could allow to improve the response obtained with this vaccine.
publishDate 2020
dc.date.none.fl_str_mv 2020
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status_str publishedVersion
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dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/286755
Recombinant mycobacterium bovis bcg is a promising platform to develop vaccines against Trypansoma Cruzi infections; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 232-232
0025-7680
CONICET Digital
CONICET
url http://hdl.handle.net/11336/286755
identifier_str_mv Recombinant mycobacterium bovis bcg is a promising platform to develop vaccines against Trypansoma Cruzi infections; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 232-232
0025-7680
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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publisher.none.fl_str_mv Fundación Revista Medicina
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