Immunization with a Chimera Consisting of the B Subunit of Shiga Toxin Type 2 and Brucella Lumazine Synthase Confers Total Protection against Shiga Toxins in Mice.

Autores: Mejias, Maria Pilar; Ghersi, Giselle; Craig, Patricio Oliver; Panek, Cecilia Analia; Bentancor, Leticia Veronica; 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. Despite the magnitude of the social impact of EHEC infections, no licensed vaccine or effective therapy is available for human use. One of the biggest challenges is to develop an effective and safe immunogen to ensure nontoxicity, as well as a strong input to the immune system to induce long-lasting, high-affinity Abs 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 on which to display foreign Ags. Taking into account the advantages of BLS and the potential capacity of the B subunit of Stx2 to induce Abs that prevent Stx2 toxicity by blocking its entrance into the host cells, we engineered a new immunogen by inserting the B subunit of Stx2 at the amino termini of BLS. The resulting chimera demonstrated a strong capacity to induce a long-lasting humoral immune response in mice. The chimera induced Abs 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 Ab development with preventive or therapeutic ends, for use in hemolytic uremic syndrome–endemic areas or during future outbreaks caused by pathogenic strains of Stx-producing E. coli.
Fil: Mejias, Maria Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina
Fil: Ghersi, Giselle. Inmunova S.a; Argentina
Fil: Craig, Patricio Oliver. Fundación Instituto Leloir; Argentina
Fil: Panek, Cecilia Analia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina
Fil: Bentancor, Leticia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina
Fil: Baschkier, Ariela. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina
Fil: Goldbaum, Fernando Alberto. Inmunova S.a; Argentina. Fundación Instituto Leloir; Argentina
Fil: Zylberman, Vanesa. Inmunova S.a; Argentina. Fundación Instituto Leloir; Argentina
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina
Materia: Hemolytic Uremic Syndrome
Shiga Toxin 2
Anti-Stx2 Antibodies
Vaccine
Nivel de accesibilidad: acceso abierto
Condiciones de uso: https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
Institución: Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador: oai:ri.conicet.gov.ar:11336/7774

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network_name_str	CONICET Digital (CONICET)
spelling	Immunization with a Chimera Consisting of the B Subunit of Shiga Toxin Type 2 and Brucella Lumazine Synthase Confers Total Protection against Shiga Toxins in Mice.Mejias, Maria PilarGhersi, GiselleCraig, Patricio OliverPanek, Cecilia AnaliaBentancor, Leticia VeronicaBaschkier, ArielaGoldbaum, Fernando AlbertoZylberman, VanesaPalermo, Marina SandraHemolytic Uremic SyndromeShiga Toxin 2Anti-Stx2 AntibodiesVaccinehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The 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. Despite the magnitude of the social impact of EHEC infections, no licensed vaccine or effective therapy is available for human use. One of the biggest challenges is to develop an effective and safe immunogen to ensure nontoxicity, as well as a strong input to the immune system to induce long-lasting, high-affinity Abs 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 on which to display foreign Ags. Taking into account the advantages of BLS and the potential capacity of the B subunit of Stx2 to induce Abs that prevent Stx2 toxicity by blocking its entrance into the host cells, we engineered a new immunogen by inserting the B subunit of Stx2 at the amino termini of BLS. The resulting chimera demonstrated a strong capacity to induce a long-lasting humoral immune response in mice. The chimera induced Abs 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 Ab development with preventive or therapeutic ends, for use in hemolytic uremic syndrome–endemic areas or during future outbreaks caused by pathogenic strains of Stx-producing E. coli.Fil: Mejias, Maria Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; ArgentinaFil: Ghersi, Giselle. Inmunova S.a; ArgentinaFil: Craig, Patricio Oliver. Fundación Instituto Leloir; ArgentinaFil: Panek, Cecilia Analia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; ArgentinaFil: Bentancor, Leticia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; ArgentinaFil: Baschkier, Ariela. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: Goldbaum, Fernando Alberto. Inmunova S.a; Argentina. Fundación Instituto Leloir; ArgentinaFil: Zylberman, Vanesa. Inmunova S.a; Argentina. Fundación Instituto Leloir; ArgentinaFil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; ArgentinaAmer Assoc Immunologists2013-09info: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/pdfapplication/pdfhttp://hdl.handle.net/11336/7774Mejias, Maria Pilar; Ghersi, Giselle; Craig, Patricio Oliver; Panek, Cecilia Analia; Bentancor, Leticia Veronica; et al.; Immunization with a Chimera Consisting of the B Subunit of Shiga Toxin Type 2 and Brucella Lumazine Synthase Confers Total Protection against Shiga Toxins in Mice.; Amer Assoc Immunologists; Journal Of Immunology; 191; 5; 9-2013; 2403-24110022-1767enginfo:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/191/5/2403.longinfo:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.4049/jimmunol.1300999info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:39Zoai:ri.conicet.gov.ar:11336/7774instacron: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:34982025-09-03 09:59:39.923CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv	Immunization with a Chimera Consisting of 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 Consisting of 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 Consisting of the B Subunit of Shiga Toxin Type 2 and Brucella Lumazine Synthase Confers Total Protection against Shiga Toxins in Mice. Mejias, Maria Pilar Hemolytic Uremic Syndrome Shiga Toxin 2 Anti-Stx2 Antibodies Vaccine
title_short	Immunization with a Chimera Consisting of 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 Consisting of 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 Consisting of 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 Consisting of 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 Consisting of 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, Maria Pilar Ghersi, Giselle Craig, Patricio Oliver Panek, Cecilia Analia Bentancor, Leticia Veronica Baschkier, Ariela Goldbaum, Fernando Alberto Zylberman, Vanesa Palermo, Marina Sandra
author	Mejias, Maria Pilar
author_facet	Mejias, Maria Pilar Ghersi, Giselle Craig, Patricio Oliver Panek, Cecilia Analia Bentancor, Leticia Veronica Baschkier, Ariela Goldbaum, Fernando Alberto Zylberman, Vanesa Palermo, Marina Sandra
author_role	author
author2	Ghersi, Giselle Craig, Patricio Oliver Panek, Cecilia Analia Bentancor, Leticia Veronica 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 Shiga Toxin 2 Anti-Stx2 Antibodies Vaccine
topic	Hemolytic Uremic Syndrome Shiga Toxin 2 Anti-Stx2 Antibodies Vaccine
purl_subject.fl_str_mv	https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1
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. Despite the magnitude of the social impact of EHEC infections, no licensed vaccine or effective therapy is available for human use. One of the biggest challenges is to develop an effective and safe immunogen to ensure nontoxicity, as well as a strong input to the immune system to induce long-lasting, high-affinity Abs 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 on which to display foreign Ags. Taking into account the advantages of BLS and the potential capacity of the B subunit of Stx2 to induce Abs that prevent Stx2 toxicity by blocking its entrance into the host cells, we engineered a new immunogen by inserting the B subunit of Stx2 at the amino termini of BLS. The resulting chimera demonstrated a strong capacity to induce a long-lasting humoral immune response in mice. The chimera induced Abs 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 Ab development with preventive or therapeutic ends, for use in hemolytic uremic syndrome–endemic areas or during future outbreaks caused by pathogenic strains of Stx-producing E. coli. Fil: Mejias, Maria Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina Fil: Ghersi, Giselle. Inmunova S.a; Argentina Fil: Craig, Patricio Oliver. Fundación Instituto Leloir; Argentina Fil: Panek, Cecilia Analia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina Fil: Bentancor, Leticia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina Fil: Baschkier, Ariela. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina Fil: Goldbaum, Fernando Alberto. Inmunova S.a; Argentina. Fundación Instituto Leloir; Argentina Fil: Zylberman, Vanesa. Inmunova S.a; Argentina. Fundación Instituto Leloir; Argentina Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. 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. Despite the magnitude of the social impact of EHEC infections, no licensed vaccine or effective therapy is available for human use. One of the biggest challenges is to develop an effective and safe immunogen to ensure nontoxicity, as well as a strong input to the immune system to induce long-lasting, high-affinity Abs 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 on which to display foreign Ags. Taking into account the advantages of BLS and the potential capacity of the B subunit of Stx2 to induce Abs that prevent Stx2 toxicity by blocking its entrance into the host cells, we engineered a new immunogen by inserting the B subunit of Stx2 at the amino termini of BLS. The resulting chimera demonstrated a strong capacity to induce a long-lasting humoral immune response in mice. The chimera induced Abs 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 Ab development with preventive or therapeutic ends, for use in hemolytic uremic syndrome–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/11336/7774 Mejias, Maria Pilar; Ghersi, Giselle; Craig, Patricio Oliver; Panek, Cecilia Analia; Bentancor, Leticia Veronica; et al.; Immunization with a Chimera Consisting of the B Subunit of Shiga Toxin Type 2 and Brucella Lumazine Synthase Confers Total Protection against Shiga Toxins in Mice.; Amer Assoc Immunologists; Journal Of Immunology; 191; 5; 9-2013; 2403-2411 0022-1767
url	http://hdl.handle.net/11336/7774
identifier_str_mv	Mejias, Maria Pilar; Ghersi, Giselle; Craig, Patricio Oliver; Panek, Cecilia Analia; Bentancor, Leticia Veronica; et al.; Immunization with a Chimera Consisting of the B Subunit of Shiga Toxin Type 2 and Brucella Lumazine Synthase Confers Total Protection against Shiga Toxins in Mice.; Amer Assoc Immunologists; Journal Of Immunology; 191; 5; 9-2013; 2403-2411 0022-1767
dc.language.none.fl_str_mv	eng
language	eng
dc.relation.none.fl_str_mv	info:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/191/5/2403.long info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.4049/jimmunol.1300999
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/
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dc.publisher.none.fl_str_mv	Amer Assoc Immunologists
publisher.none.fl_str_mv	Amer Assoc Immunologists
dc.source.none.fl_str_mv	reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str	CONICET Digital (CONICET)
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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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Immunization with a Chimera Consisting of the B Subunit of Shiga Toxin Type 2 and Brucella Lumazine Synthase Confers Total Protection against Shiga Toxins in Mice.

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