Immunization with a chimera between the B subunit of Shiga toxin type 2 and Brucella Lumazine Synthase confers total protection against Shiga toxins in mice

Autores
Mejias, María Pilar; Ghersi, Giselle; Craig, Patricio Oliver; Panek, Cecilia Analía; Bentancor, Leticia Verónica; Baschkier, Ariela; Goldbaum, Fernando Alberto; Zylberman, Vanesa; Palermo, Marina Sandra
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The striking feature of Enterohemorrhagic Escherichia coli (EHEC) infections is the production of Shiga toxins (Stx) implicated in the development of the life-threatening hemolytic uremic syndrome (HUS). Despite the magnitude of the social impact of EHEC infections, no licensed vaccine or effective therapy is presently available for human use. One of the biggest challenges is to develop an effective and safe immunogen to ensure non toxicity but also a strong input to the immune system to induce long-lasting, high affinity antibodies with anti-Stx neutralizing capacity. The enzyme lumazine synthase from Brucella spp. (BLS) is a highly stable dimer of pentamers and a scaffold with enormous plasticity for displaying foreign antigens on it. Taking into account BLS advantages and the potential capacity of the B subunit of Stx2 (Stx2B) to induce antibodies that prevent Stx2 toxicity by blocking its entrance to the host cells, we engineered a new immunogen inserting Stx2B at the amino termini of BLS. The resulting chimera demonstrated a strong capacity to induce long-lasting humoral immune response in mice. The chimera induced antibodies with high neutralizing capacity for Stx2 and its variants. Moreover, immunized mice were completely protected against i.v. Stx2-challenge and weaned mice receiving an oral challenge with EHEC were completely protected by the transference of immune sera. We conclude that this novel immunogen represents a promising candidate for vaccine or antibody development with preventive or therapeutic ends, for use in HUS endemic areas or during future outbreaks caused by pathogenic strains of Stx-producing E. coli.
Fil: Mejias, María Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Ghersi, Giselle. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Craig, Patricio Oliver. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Panek, Cecilia Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bentancor, Leticia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Baschkier, Ariela. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud; Argentina
Fil: Goldbaum, Fernando Alberto. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Zylberman, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Inmunova S.A; Argentina
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
Hemolytic Uremic Syndrome
Anti-Stx2 Antibodies
Vaccine
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:11336/20877
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/20877
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Immunization with a chimera between the B subunit of Shiga toxin type 2 and Brucella Lumazine Synthase confers total protection against Shiga toxins in miceMejias, María PilarGhersi, GiselleCraig, Patricio OliverPanek, Cecilia AnalíaBentancor, Leticia VerónicaBaschkier, ArielaGoldbaum, Fernando AlbertoZylberman, VanesaPalermo, Marina SandraHemolytic Uremic SyndromeAnti-Stx2 AntibodiesVaccinehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The striking feature of Enterohemorrhagic Escherichia coli (EHEC) infections is the production of Shiga toxins (Stx) implicated in the development of the life-threatening hemolytic uremic syndrome (HUS). Despite the magnitude of the social impact of EHEC infections, no licensed vaccine or effective therapy is presently available for human use. One of the biggest challenges is to develop an effective and safe immunogen to ensure non toxicity but also a strong input to the immune system to induce long-lasting, high affinity antibodies with anti-Stx neutralizing capacity. The enzyme lumazine synthase from Brucella spp. (BLS) is a highly stable dimer of pentamers and a scaffold with enormous plasticity for displaying foreign antigens on it. Taking into account BLS advantages and the potential capacity of the B subunit of Stx2 (Stx2B) to induce antibodies that prevent Stx2 toxicity by blocking its entrance to the host cells, we engineered a new immunogen inserting Stx2B at the amino termini of BLS. The resulting chimera demonstrated a strong capacity to induce long-lasting humoral immune response in mice. The chimera induced antibodies with high neutralizing capacity for Stx2 and its variants. Moreover, immunized mice were completely protected against i.v. Stx2-challenge and weaned mice receiving an oral challenge with EHEC were completely protected by the transference of immune sera. We conclude that this novel immunogen represents a promising candidate for vaccine or antibody development with preventive or therapeutic ends, for use in HUS endemic areas or during future outbreaks caused by pathogenic strains of Stx-producing E. coli.Fil: Mejias, María Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Ghersi, Giselle. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Craig, Patricio Oliver. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Panek, Cecilia Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bentancor, Leticia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Baschkier, Ariela. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud; ArgentinaFil: Goldbaum, Fernando Alberto. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Zylberman, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Inmunova S.A; ArgentinaFil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaAmerican Association of Immunologists2013-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/20877Mejias, María Pilar; Ghersi, Giselle; Craig, Patricio Oliver; Panek, Cecilia Analía; Bentancor, Leticia Verónica; et al.; Immunization with a chimera between the B subunit of Shiga toxin type 2 and Brucella Lumazine Synthase confers total protection against Shiga toxins in mice; American Association of Immunologists; Journal of Immunology; 191; 5; 9-2013; 2403-24110022-17671550-6606CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.1300999info:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/191/5/2403info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:46:24Zoai:ri.conicet.gov.ar:11336/20877instacron: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 09:46:24.344CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Immunization with a chimera between the B subunit of Shiga toxin type 2 and Brucella Lumazine Synthase confers total protection against Shiga toxins in mice
title Immunization with a chimera between the B subunit of Shiga toxin type 2 and Brucella Lumazine Synthase confers total protection against Shiga toxins in mice
spellingShingle Immunization with a chimera between the B subunit of Shiga toxin type 2 and Brucella Lumazine Synthase confers total protection against Shiga toxins in mice
Mejias, María Pilar
Hemolytic Uremic Syndrome
Anti-Stx2 Antibodies
Vaccine
title_short Immunization with a chimera between the B subunit of Shiga toxin type 2 and Brucella Lumazine Synthase confers total protection against Shiga toxins in mice
title_full Immunization with a chimera between the B subunit of Shiga toxin type 2 and Brucella Lumazine Synthase confers total protection against Shiga toxins in mice
title_fullStr Immunization with a chimera between the B subunit of Shiga toxin type 2 and Brucella Lumazine Synthase confers total protection against Shiga toxins in mice
title_full_unstemmed Immunization with a chimera between the B subunit of Shiga toxin type 2 and Brucella Lumazine Synthase confers total protection against Shiga toxins in mice
title_sort Immunization with a chimera between the B subunit of Shiga toxin type 2 and Brucella Lumazine Synthase confers total protection against Shiga toxins in mice
dc.creator.none.fl_str_mv Mejias, María Pilar
Ghersi, Giselle
Craig, Patricio Oliver
Panek, Cecilia Analía
Bentancor, Leticia Verónica
Baschkier, Ariela
Goldbaum, Fernando Alberto
Zylberman, Vanesa
Palermo, Marina Sandra
author Mejias, María Pilar
author_facet Mejias, María Pilar
Ghersi, Giselle
Craig, Patricio Oliver
Panek, Cecilia Analía
Bentancor, Leticia Verónica
Baschkier, Ariela
Goldbaum, Fernando Alberto
Zylberman, Vanesa
Palermo, Marina Sandra
author_role author
author2 Ghersi, Giselle
Craig, Patricio Oliver
Panek, Cecilia Analía
Bentancor, Leticia Verónica
Baschkier, Ariela
Goldbaum, Fernando Alberto
Zylberman, Vanesa
Palermo, Marina Sandra
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hemolytic Uremic Syndrome
Anti-Stx2 Antibodies
Vaccine
topic Hemolytic Uremic Syndrome
Anti-Stx2 Antibodies
Vaccine
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The striking feature of Enterohemorrhagic Escherichia coli (EHEC) infections is the production of Shiga toxins (Stx) implicated in the development of the life-threatening hemolytic uremic syndrome (HUS). Despite the magnitude of the social impact of EHEC infections, no licensed vaccine or effective therapy is presently available for human use. One of the biggest challenges is to develop an effective and safe immunogen to ensure non toxicity but also a strong input to the immune system to induce long-lasting, high affinity antibodies with anti-Stx neutralizing capacity. The enzyme lumazine synthase from Brucella spp. (BLS) is a highly stable dimer of pentamers and a scaffold with enormous plasticity for displaying foreign antigens on it. Taking into account BLS advantages and the potential capacity of the B subunit of Stx2 (Stx2B) to induce antibodies that prevent Stx2 toxicity by blocking its entrance to the host cells, we engineered a new immunogen inserting Stx2B at the amino termini of BLS. The resulting chimera demonstrated a strong capacity to induce long-lasting humoral immune response in mice. The chimera induced antibodies with high neutralizing capacity for Stx2 and its variants. Moreover, immunized mice were completely protected against i.v. Stx2-challenge and weaned mice receiving an oral challenge with EHEC were completely protected by the transference of immune sera. We conclude that this novel immunogen represents a promising candidate for vaccine or antibody development with preventive or therapeutic ends, for use in HUS endemic areas or during future outbreaks caused by pathogenic strains of Stx-producing E. coli.
Fil: Mejias, María Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Ghersi, Giselle. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Craig, Patricio Oliver. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Panek, Cecilia Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bentancor, Leticia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Baschkier, Ariela. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud; Argentina
Fil: Goldbaum, Fernando Alberto. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Zylberman, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Inmunova S.A; Argentina
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description The striking feature of Enterohemorrhagic Escherichia coli (EHEC) infections is the production of Shiga toxins (Stx) implicated in the development of the life-threatening hemolytic uremic syndrome (HUS). Despite the magnitude of the social impact of EHEC infections, no licensed vaccine or effective therapy is presently available for human use. One of the biggest challenges is to develop an effective and safe immunogen to ensure non toxicity but also a strong input to the immune system to induce long-lasting, high affinity antibodies with anti-Stx neutralizing capacity. The enzyme lumazine synthase from Brucella spp. (BLS) is a highly stable dimer of pentamers and a scaffold with enormous plasticity for displaying foreign antigens on it. Taking into account BLS advantages and the potential capacity of the B subunit of Stx2 (Stx2B) to induce antibodies that prevent Stx2 toxicity by blocking its entrance to the host cells, we engineered a new immunogen inserting Stx2B at the amino termini of BLS. The resulting chimera demonstrated a strong capacity to induce long-lasting humoral immune response in mice. The chimera induced antibodies with high neutralizing capacity for Stx2 and its variants. Moreover, immunized mice were completely protected against i.v. Stx2-challenge and weaned mice receiving an oral challenge with EHEC were completely protected by the transference of immune sera. We conclude that this novel immunogen represents a promising candidate for vaccine or antibody development with preventive or therapeutic ends, for use in HUS endemic areas or during future outbreaks caused by pathogenic strains of Stx-producing E. coli.
publishDate 2013
dc.date.none.fl_str_mv 2013-09
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/11336/20877
Mejias, María Pilar; Ghersi, Giselle; Craig, Patricio Oliver; Panek, Cecilia Analía; Bentancor, Leticia Verónica; et al.; Immunization with a chimera between the B subunit of Shiga toxin type 2 and Brucella Lumazine Synthase confers total protection against Shiga toxins in mice; American Association of Immunologists; Journal of Immunology; 191; 5; 9-2013; 2403-2411
0022-1767
1550-6606
CONICET Digital
CONICET
url http://hdl.handle.net/11336/20877
identifier_str_mv Mejias, María Pilar; Ghersi, Giselle; Craig, Patricio Oliver; Panek, Cecilia Analía; Bentancor, Leticia Verónica; et al.; Immunization with a chimera between the B subunit of Shiga toxin type 2 and Brucella Lumazine Synthase confers total protection against Shiga toxins in mice; American Association of Immunologists; Journal of Immunology; 191; 5; 9-2013; 2403-2411
0022-1767
1550-6606
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.1300999
info:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/191/5/2403
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
dc.publisher.none.fl_str_mv American Association of Immunologists
publisher.none.fl_str_mv American Association of Immunologists
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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