Oral Vaccination with Salmonella enterica as a Cruzipain-DNA Delivery System Confers Protective Immunity against Trypanosoma cruzi

Autores
Cazorla, Silvia Ines; Becker, Pablo D.; Frank, Fernanda María; Ebensen, Thomas; Sartori, María J.; Corral, Ricardo Santiago; Malchiodi, Emilio Luis; Guzman, Carlos A.
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
To stimulate both local and systemic immune responses against Trypanosoma cruzi, Salmonella enterica serovar Typhimurium aroA was exploited as DNA delivery system for cruzipain (SCz). In a murine model we compared SCz alone (GI) or co-administered with Salmonella carrying a plasmid encoding GM-CSF (GII), as well as protocols in which SCz priming was followed by boosting with recombinant cruzipain (rCz) add-mixed with either CpG-ODN (GIII) or MALP-2 (GIV). The results showed that protocols including four oral dosis of SCz (GI), elicited mainly a mucosal response characterized by IgA secretion and proliferation of GALT cells, with weak systemic responses. In contrast, the protocol including boost with rCz+CpG (GIII) triggered stronger systemic responses in terms of Cz-specific serum IgG titers, splenocytes proliferation and INF-ã secretion, and delayed type hypersensitivity response. Trypomastigote challenge of vaccinated mice resulted in significant lower levels of parasitemia respect to controls. Protection was abolished by depletion of either CD4+ or CD8+ T cells. Parasite control was also evident from the reduction of tissue damage, as revealed by histopathologic studies and serum levels of enzymes which are markers of muscle injury in chronic Chagas disease (i.e., creatine kinase, aspartate aminotransferase and lactate dehydrogenase). Enhanced release of IFN-ã and IL-2 was observed in GI and GII upon re-stimulation of splenocytes on the non-parasitic phase of infection. Our results indicate that Salmonella-mediated delivery of Cz-DNA by itself promotes the elicitation of an immune response that controls T. cruzi infection, thereby reducing parasite loads and subsequent damage to muscle tissues.
Fil: Cazorla, Silvia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Becker, Pablo D.. Helmholtz Centre for Infection Research; Alemania
Fil: Frank, Fernanda María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Ebensen, Thomas. Helmholtz Centre for Infection Research; Alemania
Fil: Sartori, María J.. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Biología Celular; Argentina
Fil: Corral, Ricardo Santiago. Hospital Zonal General de Agudos doctor Ricardo Gutierrez ; Gobierno de la Provincia de Buenos Aires; . Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Malchiodi, Emilio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Guzman, Carlos A.. Helmholtz Centre for Infection Research; Alemania
Materia
TRYPANOSOMA CRUZI
DNA VACCINE
CRUZIPAIN
SALMONELLA DELIVERY SYSTEM
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
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oai:ri.conicet.gov.ar:11336/244783
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Oral Vaccination with Salmonella enterica as a Cruzipain-DNA Delivery System Confers Protective Immunity against Trypanosoma cruziCazorla, Silvia InesBecker, Pablo D.Frank, Fernanda MaríaEbensen, ThomasSartori, María J.Corral, Ricardo SantiagoMalchiodi, Emilio LuisGuzman, Carlos A.TRYPANOSOMA CRUZIDNA VACCINECRUZIPAINSALMONELLA DELIVERY SYSTEMhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1To stimulate both local and systemic immune responses against Trypanosoma cruzi, Salmonella enterica serovar Typhimurium aroA was exploited as DNA delivery system for cruzipain (SCz). In a murine model we compared SCz alone (GI) or co-administered with Salmonella carrying a plasmid encoding GM-CSF (GII), as well as protocols in which SCz priming was followed by boosting with recombinant cruzipain (rCz) add-mixed with either CpG-ODN (GIII) or MALP-2 (GIV). The results showed that protocols including four oral dosis of SCz (GI), elicited mainly a mucosal response characterized by IgA secretion and proliferation of GALT cells, with weak systemic responses. In contrast, the protocol including boost with rCz+CpG (GIII) triggered stronger systemic responses in terms of Cz-specific serum IgG titers, splenocytes proliferation and INF-ã secretion, and delayed type hypersensitivity response. Trypomastigote challenge of vaccinated mice resulted in significant lower levels of parasitemia respect to controls. Protection was abolished by depletion of either CD4+ or CD8+ T cells. Parasite control was also evident from the reduction of tissue damage, as revealed by histopathologic studies and serum levels of enzymes which are markers of muscle injury in chronic Chagas disease (i.e., creatine kinase, aspartate aminotransferase and lactate dehydrogenase). Enhanced release of IFN-ã and IL-2 was observed in GI and GII upon re-stimulation of splenocytes on the non-parasitic phase of infection. Our results indicate that Salmonella-mediated delivery of Cz-DNA by itself promotes the elicitation of an immune response that controls T. cruzi infection, thereby reducing parasite loads and subsequent damage to muscle tissues.Fil: Cazorla, Silvia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Becker, Pablo D.. Helmholtz Centre for Infection Research; AlemaniaFil: Frank, Fernanda María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Ebensen, Thomas. Helmholtz Centre for Infection Research; AlemaniaFil: Sartori, María J.. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Biología Celular; ArgentinaFil: Corral, Ricardo Santiago. Hospital Zonal General de Agudos doctor Ricardo Gutierrez ; Gobierno de la Provincia de Buenos Aires; . Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Malchiodi, Emilio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Guzman, Carlos A.. Helmholtz Centre for Infection Research; AlemaniaAmerican Society for Microbiology2008-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/244783Cazorla, Silvia Ines; Becker, Pablo D.; Frank, Fernanda María; Ebensen, Thomas; Sartori, María J.; et al.; Oral Vaccination with Salmonella enterica as a Cruzipain-DNA Delivery System Confers Protective Immunity against Trypanosoma cruzi; American Society for Microbiology; Infection and Immunity; 76; 1; 1-2008; 324-3330019-9567CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1128/iai.01163-07info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:46:11Zoai:ri.conicet.gov.ar:11336/244783instacron: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:34982025-09-29 09:46:12.018CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Oral Vaccination with Salmonella enterica as a Cruzipain-DNA Delivery System Confers Protective Immunity against Trypanosoma cruzi
title Oral Vaccination with Salmonella enterica as a Cruzipain-DNA Delivery System Confers Protective Immunity against Trypanosoma cruzi
spellingShingle Oral Vaccination with Salmonella enterica as a Cruzipain-DNA Delivery System Confers Protective Immunity against Trypanosoma cruzi
Cazorla, Silvia Ines
TRYPANOSOMA CRUZI
DNA VACCINE
CRUZIPAIN
SALMONELLA DELIVERY SYSTEM
title_short Oral Vaccination with Salmonella enterica as a Cruzipain-DNA Delivery System Confers Protective Immunity against Trypanosoma cruzi
title_full Oral Vaccination with Salmonella enterica as a Cruzipain-DNA Delivery System Confers Protective Immunity against Trypanosoma cruzi
title_fullStr Oral Vaccination with Salmonella enterica as a Cruzipain-DNA Delivery System Confers Protective Immunity against Trypanosoma cruzi
title_full_unstemmed Oral Vaccination with Salmonella enterica as a Cruzipain-DNA Delivery System Confers Protective Immunity against Trypanosoma cruzi
title_sort Oral Vaccination with Salmonella enterica as a Cruzipain-DNA Delivery System Confers Protective Immunity against Trypanosoma cruzi
dc.creator.none.fl_str_mv Cazorla, Silvia Ines
Becker, Pablo D.
Frank, Fernanda María
Ebensen, Thomas
Sartori, María J.
Corral, Ricardo Santiago
Malchiodi, Emilio Luis
Guzman, Carlos A.
author Cazorla, Silvia Ines
author_facet Cazorla, Silvia Ines
Becker, Pablo D.
Frank, Fernanda María
Ebensen, Thomas
Sartori, María J.
Corral, Ricardo Santiago
Malchiodi, Emilio Luis
Guzman, Carlos A.
author_role author
author2 Becker, Pablo D.
Frank, Fernanda María
Ebensen, Thomas
Sartori, María J.
Corral, Ricardo Santiago
Malchiodi, Emilio Luis
Guzman, Carlos A.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv TRYPANOSOMA CRUZI
DNA VACCINE
CRUZIPAIN
SALMONELLA DELIVERY SYSTEM
topic TRYPANOSOMA CRUZI
DNA VACCINE
CRUZIPAIN
SALMONELLA DELIVERY SYSTEM
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv To stimulate both local and systemic immune responses against Trypanosoma cruzi, Salmonella enterica serovar Typhimurium aroA was exploited as DNA delivery system for cruzipain (SCz). In a murine model we compared SCz alone (GI) or co-administered with Salmonella carrying a plasmid encoding GM-CSF (GII), as well as protocols in which SCz priming was followed by boosting with recombinant cruzipain (rCz) add-mixed with either CpG-ODN (GIII) or MALP-2 (GIV). The results showed that protocols including four oral dosis of SCz (GI), elicited mainly a mucosal response characterized by IgA secretion and proliferation of GALT cells, with weak systemic responses. In contrast, the protocol including boost with rCz+CpG (GIII) triggered stronger systemic responses in terms of Cz-specific serum IgG titers, splenocytes proliferation and INF-ã secretion, and delayed type hypersensitivity response. Trypomastigote challenge of vaccinated mice resulted in significant lower levels of parasitemia respect to controls. Protection was abolished by depletion of either CD4+ or CD8+ T cells. Parasite control was also evident from the reduction of tissue damage, as revealed by histopathologic studies and serum levels of enzymes which are markers of muscle injury in chronic Chagas disease (i.e., creatine kinase, aspartate aminotransferase and lactate dehydrogenase). Enhanced release of IFN-ã and IL-2 was observed in GI and GII upon re-stimulation of splenocytes on the non-parasitic phase of infection. Our results indicate that Salmonella-mediated delivery of Cz-DNA by itself promotes the elicitation of an immune response that controls T. cruzi infection, thereby reducing parasite loads and subsequent damage to muscle tissues.
Fil: Cazorla, Silvia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Becker, Pablo D.. Helmholtz Centre for Infection Research; Alemania
Fil: Frank, Fernanda María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Ebensen, Thomas. Helmholtz Centre for Infection Research; Alemania
Fil: Sartori, María J.. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Biología Celular; Argentina
Fil: Corral, Ricardo Santiago. Hospital Zonal General de Agudos doctor Ricardo Gutierrez ; Gobierno de la Provincia de Buenos Aires; . Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Malchiodi, Emilio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Guzman, Carlos A.. Helmholtz Centre for Infection Research; Alemania
description To stimulate both local and systemic immune responses against Trypanosoma cruzi, Salmonella enterica serovar Typhimurium aroA was exploited as DNA delivery system for cruzipain (SCz). In a murine model we compared SCz alone (GI) or co-administered with Salmonella carrying a plasmid encoding GM-CSF (GII), as well as protocols in which SCz priming was followed by boosting with recombinant cruzipain (rCz) add-mixed with either CpG-ODN (GIII) or MALP-2 (GIV). The results showed that protocols including four oral dosis of SCz (GI), elicited mainly a mucosal response characterized by IgA secretion and proliferation of GALT cells, with weak systemic responses. In contrast, the protocol including boost with rCz+CpG (GIII) triggered stronger systemic responses in terms of Cz-specific serum IgG titers, splenocytes proliferation and INF-ã secretion, and delayed type hypersensitivity response. Trypomastigote challenge of vaccinated mice resulted in significant lower levels of parasitemia respect to controls. Protection was abolished by depletion of either CD4+ or CD8+ T cells. Parasite control was also evident from the reduction of tissue damage, as revealed by histopathologic studies and serum levels of enzymes which are markers of muscle injury in chronic Chagas disease (i.e., creatine kinase, aspartate aminotransferase and lactate dehydrogenase). Enhanced release of IFN-ã and IL-2 was observed in GI and GII upon re-stimulation of splenocytes on the non-parasitic phase of infection. Our results indicate that Salmonella-mediated delivery of Cz-DNA by itself promotes the elicitation of an immune response that controls T. cruzi infection, thereby reducing parasite loads and subsequent damage to muscle tissues.
publishDate 2008
dc.date.none.fl_str_mv 2008-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/244783
Cazorla, Silvia Ines; Becker, Pablo D.; Frank, Fernanda María; Ebensen, Thomas; Sartori, María J.; et al.; Oral Vaccination with Salmonella enterica as a Cruzipain-DNA Delivery System Confers Protective Immunity against Trypanosoma cruzi; American Society for Microbiology; Infection and Immunity; 76; 1; 1-2008; 324-333
0019-9567
CONICET Digital
CONICET
url http://hdl.handle.net/11336/244783
identifier_str_mv Cazorla, Silvia Ines; Becker, Pablo D.; Frank, Fernanda María; Ebensen, Thomas; Sartori, María J.; et al.; Oral Vaccination with Salmonella enterica as a Cruzipain-DNA Delivery System Confers Protective Immunity against Trypanosoma cruzi; American Society for Microbiology; Infection and Immunity; 76; 1; 1-2008; 324-333
0019-9567
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1128/iai.01163-07
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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