Salmonella enterica serovar typhimurium vaccine strains expressing a nontoxic shiga-like toxin 2 derivative induce partial protective immunity to the toxin expressed by enterohemor...

Autores
Rojas, Robert L.G.; Gomes, Priscila A.D.P.; Bentancor, Leticia Verónica; Sbrogio Almeida, Maria E.; Costa, Sérgio O. P.; Massis, Liliana M.; Ferreira, Rita C. C.; Palermo, Marina Sandra; Ferreira, Luís C. S.
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Shiga-like toxin 2 (Stx2)-producing enterohemorrhagic Escherichia coli (referred to as EHEC or STEC) strains are the primary etiologic agents of hemolytic-uremic syndrome (HUS), which leads to renal failure and high mortality rates. Expression of Stx2 is the most relevant virulence-associated factor of EHEC strains, and toxin neutralization by antigen-specific serum antibodies represents the main target for both preventive and therapeutic anti-HUS approaches. In the present report, we describe two Salmonella enterica serovar Typhimurium aroA vaccine strains expressing a nontoxic plasmid-encoded derivative of Stx2 (Stx2δAB) containing the complete nontoxic A2 subunit and the receptor binding B subunit. The two S. Typhimurium strains differ in the expression of flagellin, the structural subunit of the flagellar shaft, which exerts strong adjuvant effects. The vaccine strains expressed Stx2δAB, either cell bound or secreted into the extracellular environment, and showed enhanced mouse gut colonization and high plasmid stability under both in vitro and in vivo conditions. Oral immunization of mice with three doses of the S. Typhimurium vaccine strains elicited serum anti-Stx2B (IgG) antibodies that neutralized the toxic effects of the native toxin under in vitro conditions (Vero cells) and conferred partial protection under in vivo conditions. No significant differences with respect to gut colonization or the induction of antigen-specific antibody responses were detected in mice vaccinated with flagellated versus nonflagellated bacterial strains. The present results indicate that expression of Stx2δAB by attenuated S. Typhimurium strains is an alternative vaccine approach for HUS control, but additional improvements in the immunogenicity of Stx2 toxoids are still required.
Fil: Rojas, Robert L.G.. Universidade de Sao Paulo; Brasil
Fil: Gomes, Priscila A.D.P.. Universidade de Sao Paulo; Brasil
Fil: Bentancor, Leticia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Sbrogio Almeida, Maria E.. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; Brasil
Fil: Costa, Sérgio O. P.. Universidade de Sao Paulo; Brasil
Fil: Massis, Liliana M.. Universidade de Sao Paulo; Brasil
Fil: Ferreira, Rita C. C.. Universidade de Sao Paulo; Brasil
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Ferreira, Luís C. S.. Universidade de Sao Paulo; Brasil
Materia
EHEC
HUS,
Stx,
S. Typhimurium;vaccines, flagellin
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:11336/92213
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/92213
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Salmonella enterica serovar typhimurium vaccine strains expressing a nontoxic shiga-like toxin 2 derivative induce partial protective immunity to the toxin expressed by enterohemorrhagic escherichia coliRojas, Robert L.G.Gomes, Priscila A.D.P.Bentancor, Leticia VerónicaSbrogio Almeida, Maria E.Costa, Sérgio O. P.Massis, Liliana M.Ferreira, Rita C. C.Palermo, Marina SandraFerreira, Luís C. S.EHECHUS,Stx,S. Typhimurium;vaccines, flagellinhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Shiga-like toxin 2 (Stx2)-producing enterohemorrhagic Escherichia coli (referred to as EHEC or STEC) strains are the primary etiologic agents of hemolytic-uremic syndrome (HUS), which leads to renal failure and high mortality rates. Expression of Stx2 is the most relevant virulence-associated factor of EHEC strains, and toxin neutralization by antigen-specific serum antibodies represents the main target for both preventive and therapeutic anti-HUS approaches. In the present report, we describe two Salmonella enterica serovar Typhimurium aroA vaccine strains expressing a nontoxic plasmid-encoded derivative of Stx2 (Stx2δAB) containing the complete nontoxic A2 subunit and the receptor binding B subunit. The two S. Typhimurium strains differ in the expression of flagellin, the structural subunit of the flagellar shaft, which exerts strong adjuvant effects. The vaccine strains expressed Stx2δAB, either cell bound or secreted into the extracellular environment, and showed enhanced mouse gut colonization and high plasmid stability under both in vitro and in vivo conditions. Oral immunization of mice with three doses of the S. Typhimurium vaccine strains elicited serum anti-Stx2B (IgG) antibodies that neutralized the toxic effects of the native toxin under in vitro conditions (Vero cells) and conferred partial protection under in vivo conditions. No significant differences with respect to gut colonization or the induction of antigen-specific antibody responses were detected in mice vaccinated with flagellated versus nonflagellated bacterial strains. The present results indicate that expression of Stx2δAB by attenuated S. Typhimurium strains is an alternative vaccine approach for HUS control, but additional improvements in the immunogenicity of Stx2 toxoids are still required.Fil: Rojas, Robert L.G.. Universidade de Sao Paulo; BrasilFil: Gomes, Priscila A.D.P.. Universidade de Sao Paulo; BrasilFil: Bentancor, Leticia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Sbrogio Almeida, Maria E.. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; BrasilFil: Costa, Sérgio O. P.. Universidade de Sao Paulo; BrasilFil: Massis, Liliana M.. Universidade de Sao Paulo; BrasilFil: Ferreira, Rita C. C.. Universidade de Sao Paulo; BrasilFil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Ferreira, Luís C. S.. Universidade de Sao Paulo; BrasilAmerican Society for Microbiology2010-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/92213Rojas, Robert L.G.; Gomes, Priscila A.D.P.; Bentancor, Leticia Verónica; Sbrogio Almeida, Maria E.; Costa, Sérgio O. P.; et al.; Salmonella enterica serovar typhimurium vaccine strains expressing a nontoxic shiga-like toxin 2 derivative induce partial protective immunity to the toxin expressed by enterohemorrhagic escherichia coli; American Society for Microbiology; Clinical and Vaccine Immunology; 17; 4; 4-2010; 529-5361556-6811CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1128/CVI.00495-09info:eu-repo/semantics/altIdentifier/url/https://cvi.asm.org/content/17/4/529info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:04:07Zoai:ri.conicet.gov.ar:11336/92213instacron: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:34982025-10-15 15:04:07.522CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Salmonella enterica serovar typhimurium vaccine strains expressing a nontoxic shiga-like toxin 2 derivative induce partial protective immunity to the toxin expressed by enterohemorrhagic escherichia coli
title Salmonella enterica serovar typhimurium vaccine strains expressing a nontoxic shiga-like toxin 2 derivative induce partial protective immunity to the toxin expressed by enterohemorrhagic escherichia coli
spellingShingle Salmonella enterica serovar typhimurium vaccine strains expressing a nontoxic shiga-like toxin 2 derivative induce partial protective immunity to the toxin expressed by enterohemorrhagic escherichia coli
Rojas, Robert L.G.
EHEC
HUS,
Stx,
S. Typhimurium;vaccines, flagellin
title_short Salmonella enterica serovar typhimurium vaccine strains expressing a nontoxic shiga-like toxin 2 derivative induce partial protective immunity to the toxin expressed by enterohemorrhagic escherichia coli
title_full Salmonella enterica serovar typhimurium vaccine strains expressing a nontoxic shiga-like toxin 2 derivative induce partial protective immunity to the toxin expressed by enterohemorrhagic escherichia coli
title_fullStr Salmonella enterica serovar typhimurium vaccine strains expressing a nontoxic shiga-like toxin 2 derivative induce partial protective immunity to the toxin expressed by enterohemorrhagic escherichia coli
title_full_unstemmed Salmonella enterica serovar typhimurium vaccine strains expressing a nontoxic shiga-like toxin 2 derivative induce partial protective immunity to the toxin expressed by enterohemorrhagic escherichia coli
title_sort Salmonella enterica serovar typhimurium vaccine strains expressing a nontoxic shiga-like toxin 2 derivative induce partial protective immunity to the toxin expressed by enterohemorrhagic escherichia coli
dc.creator.none.fl_str_mv Rojas, Robert L.G.
Gomes, Priscila A.D.P.
Bentancor, Leticia Verónica
Sbrogio Almeida, Maria E.
Costa, Sérgio O. P.
Massis, Liliana M.
Ferreira, Rita C. C.
Palermo, Marina Sandra
Ferreira, Luís C. S.
author Rojas, Robert L.G.
author_facet Rojas, Robert L.G.
Gomes, Priscila A.D.P.
Bentancor, Leticia Verónica
Sbrogio Almeida, Maria E.
Costa, Sérgio O. P.
Massis, Liliana M.
Ferreira, Rita C. C.
Palermo, Marina Sandra
Ferreira, Luís C. S.
author_role author
author2 Gomes, Priscila A.D.P.
Bentancor, Leticia Verónica
Sbrogio Almeida, Maria E.
Costa, Sérgio O. P.
Massis, Liliana M.
Ferreira, Rita C. C.
Palermo, Marina Sandra
Ferreira, Luís C. S.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv EHEC
HUS,
Stx,
S. Typhimurium;vaccines, flagellin
topic EHEC
HUS,
Stx,
S. Typhimurium;vaccines, flagellin
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Shiga-like toxin 2 (Stx2)-producing enterohemorrhagic Escherichia coli (referred to as EHEC or STEC) strains are the primary etiologic agents of hemolytic-uremic syndrome (HUS), which leads to renal failure and high mortality rates. Expression of Stx2 is the most relevant virulence-associated factor of EHEC strains, and toxin neutralization by antigen-specific serum antibodies represents the main target for both preventive and therapeutic anti-HUS approaches. In the present report, we describe two Salmonella enterica serovar Typhimurium aroA vaccine strains expressing a nontoxic plasmid-encoded derivative of Stx2 (Stx2δAB) containing the complete nontoxic A2 subunit and the receptor binding B subunit. The two S. Typhimurium strains differ in the expression of flagellin, the structural subunit of the flagellar shaft, which exerts strong adjuvant effects. The vaccine strains expressed Stx2δAB, either cell bound or secreted into the extracellular environment, and showed enhanced mouse gut colonization and high plasmid stability under both in vitro and in vivo conditions. Oral immunization of mice with three doses of the S. Typhimurium vaccine strains elicited serum anti-Stx2B (IgG) antibodies that neutralized the toxic effects of the native toxin under in vitro conditions (Vero cells) and conferred partial protection under in vivo conditions. No significant differences with respect to gut colonization or the induction of antigen-specific antibody responses were detected in mice vaccinated with flagellated versus nonflagellated bacterial strains. The present results indicate that expression of Stx2δAB by attenuated S. Typhimurium strains is an alternative vaccine approach for HUS control, but additional improvements in the immunogenicity of Stx2 toxoids are still required.
Fil: Rojas, Robert L.G.. Universidade de Sao Paulo; Brasil
Fil: Gomes, Priscila A.D.P.. Universidade de Sao Paulo; Brasil
Fil: Bentancor, Leticia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Sbrogio Almeida, Maria E.. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; Brasil
Fil: Costa, Sérgio O. P.. Universidade de Sao Paulo; Brasil
Fil: Massis, Liliana M.. Universidade de Sao Paulo; Brasil
Fil: Ferreira, Rita C. C.. Universidade de Sao Paulo; Brasil
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Ferreira, Luís C. S.. Universidade de Sao Paulo; Brasil
description Shiga-like toxin 2 (Stx2)-producing enterohemorrhagic Escherichia coli (referred to as EHEC or STEC) strains are the primary etiologic agents of hemolytic-uremic syndrome (HUS), which leads to renal failure and high mortality rates. Expression of Stx2 is the most relevant virulence-associated factor of EHEC strains, and toxin neutralization by antigen-specific serum antibodies represents the main target for both preventive and therapeutic anti-HUS approaches. In the present report, we describe two Salmonella enterica serovar Typhimurium aroA vaccine strains expressing a nontoxic plasmid-encoded derivative of Stx2 (Stx2δAB) containing the complete nontoxic A2 subunit and the receptor binding B subunit. The two S. Typhimurium strains differ in the expression of flagellin, the structural subunit of the flagellar shaft, which exerts strong adjuvant effects. The vaccine strains expressed Stx2δAB, either cell bound or secreted into the extracellular environment, and showed enhanced mouse gut colonization and high plasmid stability under both in vitro and in vivo conditions. Oral immunization of mice with three doses of the S. Typhimurium vaccine strains elicited serum anti-Stx2B (IgG) antibodies that neutralized the toxic effects of the native toxin under in vitro conditions (Vero cells) and conferred partial protection under in vivo conditions. No significant differences with respect to gut colonization or the induction of antigen-specific antibody responses were detected in mice vaccinated with flagellated versus nonflagellated bacterial strains. The present results indicate that expression of Stx2δAB by attenuated S. Typhimurium strains is an alternative vaccine approach for HUS control, but additional improvements in the immunogenicity of Stx2 toxoids are still required.
publishDate 2010
dc.date.none.fl_str_mv 2010-04
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/11336/92213
Rojas, Robert L.G.; Gomes, Priscila A.D.P.; Bentancor, Leticia Verónica; Sbrogio Almeida, Maria E.; Costa, Sérgio O. P.; et al.; Salmonella enterica serovar typhimurium vaccine strains expressing a nontoxic shiga-like toxin 2 derivative induce partial protective immunity to the toxin expressed by enterohemorrhagic escherichia coli; American Society for Microbiology; Clinical and Vaccine Immunology; 17; 4; 4-2010; 529-536
1556-6811
CONICET Digital
CONICET
url http://hdl.handle.net/11336/92213
identifier_str_mv Rojas, Robert L.G.; Gomes, Priscila A.D.P.; Bentancor, Leticia Verónica; Sbrogio Almeida, Maria E.; Costa, Sérgio O. P.; et al.; Salmonella enterica serovar typhimurium vaccine strains expressing a nontoxic shiga-like toxin 2 derivative induce partial protective immunity to the toxin expressed by enterohemorrhagic escherichia coli; American Society for Microbiology; Clinical and Vaccine Immunology; 17; 4; 4-2010; 529-536
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.00495-09
info:eu-repo/semantics/altIdentifier/url/https://cvi.asm.org/content/17/4/529
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 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 13.22299

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