A DNA vaccine encoding the enterohemorragic Escherichia coli shiga-like toxin 2 A2 and B subunits confers protective immunity to shiga toxin challenge in the murine model

Autores
Bentancor, Leticia Verónica; Bilen, Marcos Fabian; Fernández Brando, Romina Jimena; Ramos, Maria Victoria; Ferreira, Luis C. S.; Ghiringhelli, Pablo Daniel; Palermo, Marina Sandra
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Production of verocytotoxin or Shiga-like toxin (Stx), particularly Stx2, is the basis of hemolytic uremic syndrome, a frequently lethal outcome for subjects infected with Stx2-producing enterohemorrhagic Escherichia coli (EHEC) strains. The toxin is formed by a single A subunit, which promotes protein synthesis inhibition in eukaryotic cells, and five B subunits, which bind to globotriaosylceramide at the surface of host cells. Host enzymes cleave the A subunit into the A1 peptide, endowed with N-glycosidase activity to the 28S rRNA, and the A2 peptide, which confers stability to the B pentamer. We report the construction of a DNA vaccine (pStx2ΔAB) that expresses a nontoxic Stx2 mutated form consisting of the last 32 amino acids of the A2 sequence and the complete B subunit as two nonfused polypeptides. Immunization trials carried out with the DNA vaccine in BALB/c mice, alone or in combination with another DNA vaccine encoding granulocyte- macrophage colony-stimulating factor, resulted in systemic Stx-specific antibody responses targeting both A and B subunits of the native Stx2. Moreover, anti-Stx2 antibodies raised in mice immunized with pStx2AAB showed toxin neutralization activity in vitro and, more importantly, conferred partial protection to Stx2 challenge in vivo. The present vector represents the second DNA vaccine so far reported to induce protective immunity to Stx2 and may contribute, either alone or in combination with other procedures, to the development of prophylactic or therapeutic interventions aiming to ameliorate EHEC infection-associated sequelae. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Fil: Bentancor, Leticia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Bilen, Marcos Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Fernández Brando, Romina Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Ramos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Ferreira, Luis C. S.. Universidade de Sao Paulo; Brasil
Fil: Ghiringhelli, Pablo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Materia
Hus
Stx2
Vaccine
Dna
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:11336/55107
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/55107
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A DNA vaccine encoding the enterohemorragic Escherichia coli shiga-like toxin 2 A2 and B subunits confers protective immunity to shiga toxin challenge in the murine modelBentancor, Leticia VerónicaBilen, Marcos FabianFernández Brando, Romina JimenaRamos, Maria VictoriaFerreira, Luis C. S.Ghiringhelli, Pablo DanielPalermo, Marina SandraHusStx2VaccineDnahttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Production of verocytotoxin or Shiga-like toxin (Stx), particularly Stx2, is the basis of hemolytic uremic syndrome, a frequently lethal outcome for subjects infected with Stx2-producing enterohemorrhagic Escherichia coli (EHEC) strains. The toxin is formed by a single A subunit, which promotes protein synthesis inhibition in eukaryotic cells, and five B subunits, which bind to globotriaosylceramide at the surface of host cells. Host enzymes cleave the A subunit into the A1 peptide, endowed with N-glycosidase activity to the 28S rRNA, and the A2 peptide, which confers stability to the B pentamer. We report the construction of a DNA vaccine (pStx2ΔAB) that expresses a nontoxic Stx2 mutated form consisting of the last 32 amino acids of the A2 sequence and the complete B subunit as two nonfused polypeptides. Immunization trials carried out with the DNA vaccine in BALB/c mice, alone or in combination with another DNA vaccine encoding granulocyte- macrophage colony-stimulating factor, resulted in systemic Stx-specific antibody responses targeting both A and B subunits of the native Stx2. Moreover, anti-Stx2 antibodies raised in mice immunized with pStx2AAB showed toxin neutralization activity in vitro and, more importantly, conferred partial protection to Stx2 challenge in vivo. The present vector represents the second DNA vaccine so far reported to induce protective immunity to Stx2 and may contribute, either alone or in combination with other procedures, to the development of prophylactic or therapeutic interventions aiming to ameliorate EHEC infection-associated sequelae. Copyright © 2009, American Society for Microbiology. All Rights Reserved.Fil: Bentancor, Leticia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Bilen, Marcos Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Fernández Brando, Romina Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaFil: Ramos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaFil: Ferreira, Luis C. S.. Universidade de Sao Paulo; BrasilFil: Ghiringhelli, Pablo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaAmerican Society for Microbiology2009-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/55107Bentancor, Leticia Verónica; Bilen, Marcos Fabian; Fernández Brando, Romina Jimena; Ramos, Maria Victoria; Ferreira, Luis C. S.; et al.; A DNA vaccine encoding the enterohemorragic Escherichia coli shiga-like toxin 2 A2 and B subunits confers protective immunity to shiga toxin challenge in the murine model; American Society for Microbiology; Clinical and Vaccine Immunology; 16; 5; 5-2009; 712-7181556-6811CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1128/CVI.00328-08info:eu-repo/semantics/altIdentifier/url/http://cvi.asm.org/content/16/5/712info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:45:56Zoai:ri.conicet.gov.ar:11336/55107instacron: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 10:45:56.867CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A DNA vaccine encoding the enterohemorragic Escherichia coli shiga-like toxin 2 A2 and B subunits confers protective immunity to shiga toxin challenge in the murine model
title A DNA vaccine encoding the enterohemorragic Escherichia coli shiga-like toxin 2 A2 and B subunits confers protective immunity to shiga toxin challenge in the murine model
spellingShingle A DNA vaccine encoding the enterohemorragic Escherichia coli shiga-like toxin 2 A2 and B subunits confers protective immunity to shiga toxin challenge in the murine model
Bentancor, Leticia Verónica
Hus
Stx2
Vaccine
Dna
title_short A DNA vaccine encoding the enterohemorragic Escherichia coli shiga-like toxin 2 A2 and B subunits confers protective immunity to shiga toxin challenge in the murine model
title_full A DNA vaccine encoding the enterohemorragic Escherichia coli shiga-like toxin 2 A2 and B subunits confers protective immunity to shiga toxin challenge in the murine model
title_fullStr A DNA vaccine encoding the enterohemorragic Escherichia coli shiga-like toxin 2 A2 and B subunits confers protective immunity to shiga toxin challenge in the murine model
title_full_unstemmed A DNA vaccine encoding the enterohemorragic Escherichia coli shiga-like toxin 2 A2 and B subunits confers protective immunity to shiga toxin challenge in the murine model
title_sort A DNA vaccine encoding the enterohemorragic Escherichia coli shiga-like toxin 2 A2 and B subunits confers protective immunity to shiga toxin challenge in the murine model
dc.creator.none.fl_str_mv Bentancor, Leticia Verónica
Bilen, Marcos Fabian
Fernández Brando, Romina Jimena
Ramos, Maria Victoria
Ferreira, Luis C. S.
Ghiringhelli, Pablo Daniel
Palermo, Marina Sandra
author Bentancor, Leticia Verónica
author_facet Bentancor, Leticia Verónica
Bilen, Marcos Fabian
Fernández Brando, Romina Jimena
Ramos, Maria Victoria
Ferreira, Luis C. S.
Ghiringhelli, Pablo Daniel
Palermo, Marina Sandra
author_role author
author2 Bilen, Marcos Fabian
Fernández Brando, Romina Jimena
Ramos, Maria Victoria
Ferreira, Luis C. S.
Ghiringhelli, Pablo Daniel
Palermo, Marina Sandra
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Hus
Stx2
Vaccine
Dna
topic Hus
Stx2
Vaccine
Dna
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Production of verocytotoxin or Shiga-like toxin (Stx), particularly Stx2, is the basis of hemolytic uremic syndrome, a frequently lethal outcome for subjects infected with Stx2-producing enterohemorrhagic Escherichia coli (EHEC) strains. The toxin is formed by a single A subunit, which promotes protein synthesis inhibition in eukaryotic cells, and five B subunits, which bind to globotriaosylceramide at the surface of host cells. Host enzymes cleave the A subunit into the A1 peptide, endowed with N-glycosidase activity to the 28S rRNA, and the A2 peptide, which confers stability to the B pentamer. We report the construction of a DNA vaccine (pStx2ΔAB) that expresses a nontoxic Stx2 mutated form consisting of the last 32 amino acids of the A2 sequence and the complete B subunit as two nonfused polypeptides. Immunization trials carried out with the DNA vaccine in BALB/c mice, alone or in combination with another DNA vaccine encoding granulocyte- macrophage colony-stimulating factor, resulted in systemic Stx-specific antibody responses targeting both A and B subunits of the native Stx2. Moreover, anti-Stx2 antibodies raised in mice immunized with pStx2AAB showed toxin neutralization activity in vitro and, more importantly, conferred partial protection to Stx2 challenge in vivo. The present vector represents the second DNA vaccine so far reported to induce protective immunity to Stx2 and may contribute, either alone or in combination with other procedures, to the development of prophylactic or therapeutic interventions aiming to ameliorate EHEC infection-associated sequelae. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Fil: Bentancor, Leticia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Bilen, Marcos Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Fernández Brando, Romina Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Ramos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Ferreira, Luis C. S.. Universidade de Sao Paulo; Brasil
Fil: Ghiringhelli, Pablo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
description Production of verocytotoxin or Shiga-like toxin (Stx), particularly Stx2, is the basis of hemolytic uremic syndrome, a frequently lethal outcome for subjects infected with Stx2-producing enterohemorrhagic Escherichia coli (EHEC) strains. The toxin is formed by a single A subunit, which promotes protein synthesis inhibition in eukaryotic cells, and five B subunits, which bind to globotriaosylceramide at the surface of host cells. Host enzymes cleave the A subunit into the A1 peptide, endowed with N-glycosidase activity to the 28S rRNA, and the A2 peptide, which confers stability to the B pentamer. We report the construction of a DNA vaccine (pStx2ΔAB) that expresses a nontoxic Stx2 mutated form consisting of the last 32 amino acids of the A2 sequence and the complete B subunit as two nonfused polypeptides. Immunization trials carried out with the DNA vaccine in BALB/c mice, alone or in combination with another DNA vaccine encoding granulocyte- macrophage colony-stimulating factor, resulted in systemic Stx-specific antibody responses targeting both A and B subunits of the native Stx2. Moreover, anti-Stx2 antibodies raised in mice immunized with pStx2AAB showed toxin neutralization activity in vitro and, more importantly, conferred partial protection to Stx2 challenge in vivo. The present vector represents the second DNA vaccine so far reported to induce protective immunity to Stx2 and may contribute, either alone or in combination with other procedures, to the development of prophylactic or therapeutic interventions aiming to ameliorate EHEC infection-associated sequelae. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
publishDate 2009
dc.date.none.fl_str_mv 2009-05
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/11336/55107
Bentancor, Leticia Verónica; Bilen, Marcos Fabian; Fernández Brando, Romina Jimena; Ramos, Maria Victoria; Ferreira, Luis C. S.; et al.; A DNA vaccine encoding the enterohemorragic Escherichia coli shiga-like toxin 2 A2 and B subunits confers protective immunity to shiga toxin challenge in the murine model; American Society for Microbiology; Clinical and Vaccine Immunology; 16; 5; 5-2009; 712-718
1556-6811
CONICET Digital
CONICET
url http://hdl.handle.net/11336/55107
identifier_str_mv Bentancor, Leticia Verónica; Bilen, Marcos Fabian; Fernández Brando, Romina Jimena; Ramos, Maria Victoria; Ferreira, Luis C. S.; et al.; A DNA vaccine encoding the enterohemorragic Escherichia coli shiga-like toxin 2 A2 and B subunits confers protective immunity to shiga toxin challenge in the murine model; American Society for Microbiology; Clinical and Vaccine Immunology; 16; 5; 5-2009; 712-718
1556-6811
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/CVI.00328-08
info:eu-repo/semantics/altIdentifier/url/http://cvi.asm.org/content/16/5/712
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
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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score 13.070432

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