Preclinical Studies of NEAST (Neutralizing Equine Anti-Shiga Toxin): A Potential Treatment for Prevention of Stec-Hus

Autores
Hiriart, Yanina; Pardo, Romina Paola; Bukata, Lucas; Lauché, Constanza Elena; Muñoz, Luciana; Berengeno, Andrea Lorena; Colonna, Mariana; Ortega, Hugo Hector; Goldbaum, Fernando Alberto; Sanguineti, Santiago; Zylberman, Vanesa
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
STEC-HUS is a clinical syndrome characterized by the triad of thrombotic microangiopathy, thrombocytopenia and acute kidney injury. Despite the magnitude of the social and economic problems caused by STEC infections, there are currently no specific therapeutic options on the market. HUS is a toxemic disorder and the therapeutic effect of the early intervention with anti-toxin neutralizing antibodies has been supported in several animal models. We have designed novel protein nanoparticles with very strong immunogenic capacity by inserting Stx1B and Stx2B subunits of Shiga toxin to Brucella abortus Lumazine Synthase (BLS). The chimeric BLS-StxBs particles elicited strong neutralizing antibodies against Shiga toxins in horses. Based on these responses, we produced NEAST (Neutralizing Equine Anti-Shiga Toxin), composed of purified F(ab’)2 fragments. In this report we present the preclinical analysis of this new treatment. As a general conclusion, NEAST shows a very strong neutralizing capacity against 8 Shiga toxin variants in preclinical models of STEC-HUS. NEAST is also able to neutralize pathologic effects after previous exposure to Shiga Toxin, defining a potential therapeutic window. Besides, NEAST shows an excellent pharmacokinetics and safety profile in animal models. Overall, these results indicate that NEAST is a very good drug candidate for preventing the onset of HUS in STEC-infected patients and validate the conduction of a first in human clinical study at the Hospital Italiano de Buenos Aires in order to evaluate its safety and pharmacokinetic profiles in healthy adult volunteers.
Fil: Hiriart, Yanina. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Pardo, Romina Paola. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bukata, Lucas. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lauché, Constanza Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Muñoz, Luciana. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Berengeno, Andrea Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Colonna, Mariana. Inmunova S.A; Argentina
Fil: Ortega, Hugo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Goldbaum, Fernando Alberto. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Sanguineti, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina. Inmunova S.A; Argentina
Fil: Zylberman, Vanesa. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Materia
Sindrome urémico hemolítico
tratamiento SUH
enfermedad renal
fragmentos F(ab')2
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:11336/174746
Acceder
id CONICETDig_b649196adf680694422dfa37c3200bb1
oai_identifier_str oai:ri.conicet.gov.ar:11336/174746
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Preclinical Studies of NEAST (Neutralizing Equine Anti-Shiga Toxin): A Potential Treatment for Prevention of Stec-HusHiriart, YaninaPardo, Romina PaolaBukata, LucasLauché, Constanza ElenaMuñoz, LucianaBerengeno, Andrea LorenaColonna, MarianaOrtega, Hugo HectorGoldbaum, Fernando AlbertoSanguineti, SantiagoZylberman, VanesaSindrome urémico hemolíticotratamiento SUHenfermedad renalfragmentos F(ab')2https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3STEC-HUS is a clinical syndrome characterized by the triad of thrombotic microangiopathy, thrombocytopenia and acute kidney injury. Despite the magnitude of the social and economic problems caused by STEC infections, there are currently no specific therapeutic options on the market. HUS is a toxemic disorder and the therapeutic effect of the early intervention with anti-toxin neutralizing antibodies has been supported in several animal models. We have designed novel protein nanoparticles with very strong immunogenic capacity by inserting Stx1B and Stx2B subunits of Shiga toxin to Brucella abortus Lumazine Synthase (BLS). The chimeric BLS-StxBs particles elicited strong neutralizing antibodies against Shiga toxins in horses. Based on these responses, we produced NEAST (Neutralizing Equine Anti-Shiga Toxin), composed of purified F(ab’)2 fragments. In this report we present the preclinical analysis of this new treatment. As a general conclusion, NEAST shows a very strong neutralizing capacity against 8 Shiga toxin variants in preclinical models of STEC-HUS. NEAST is also able to neutralize pathologic effects after previous exposure to Shiga Toxin, defining a potential therapeutic window. Besides, NEAST shows an excellent pharmacokinetics and safety profile in animal models. Overall, these results indicate that NEAST is a very good drug candidate for preventing the onset of HUS in STEC-infected patients and validate the conduction of a first in human clinical study at the Hospital Italiano de Buenos Aires in order to evaluate its safety and pharmacokinetic profiles in healthy adult volunteers.Fil: Hiriart, Yanina. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Pardo, Romina Paola. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bukata, Lucas. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lauché, Constanza Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Muñoz, Luciana. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Berengeno, Andrea Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Colonna, Mariana. Inmunova S.A; ArgentinaFil: Ortega, Hugo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Goldbaum, Fernando Alberto. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Sanguineti, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina. Inmunova S.A; ArgentinaFil: Zylberman, Vanesa. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaInsight Medical Publishing2019-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/174746Hiriart, Yanina; Pardo, Romina Paola; Bukata, Lucas; Lauché, Constanza Elena; Muñoz, Luciana; et al.; Preclinical Studies of NEAST (Neutralizing Equine Anti-Shiga Toxin): A Potential Treatment for Prevention of Stec-Hus; Insight Medical Publishing; International Journal of Drug Development and Research; 11; 3; 9-2019; 15-24CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.ijddr.in/drug-development/preclinicalstudies-of-neast-neutralizing-equine-antishiga-to-xin-apotential-treatment-for-prevention-of-stechus.php?aid=24641info:eu-repo/semantics/altIdentifier/doi/10.36648/0975-9344.11.3.140info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:33:10Zoai:ri.conicet.gov.ar:11336/174746instacron: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:34982025-10-22 11:33:11.232CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Preclinical Studies of NEAST (Neutralizing Equine Anti-Shiga Toxin): A Potential Treatment for Prevention of Stec-Hus
title Preclinical Studies of NEAST (Neutralizing Equine Anti-Shiga Toxin): A Potential Treatment for Prevention of Stec-Hus
spellingShingle Preclinical Studies of NEAST (Neutralizing Equine Anti-Shiga Toxin): A Potential Treatment for Prevention of Stec-Hus
Hiriart, Yanina
Sindrome urémico hemolítico
tratamiento SUH
enfermedad renal
fragmentos F(ab')2
title_short Preclinical Studies of NEAST (Neutralizing Equine Anti-Shiga Toxin): A Potential Treatment for Prevention of Stec-Hus
title_full Preclinical Studies of NEAST (Neutralizing Equine Anti-Shiga Toxin): A Potential Treatment for Prevention of Stec-Hus
title_fullStr Preclinical Studies of NEAST (Neutralizing Equine Anti-Shiga Toxin): A Potential Treatment for Prevention of Stec-Hus
title_full_unstemmed Preclinical Studies of NEAST (Neutralizing Equine Anti-Shiga Toxin): A Potential Treatment for Prevention of Stec-Hus
title_sort Preclinical Studies of NEAST (Neutralizing Equine Anti-Shiga Toxin): A Potential Treatment for Prevention of Stec-Hus
dc.creator.none.fl_str_mv Hiriart, Yanina
Pardo, Romina Paola
Bukata, Lucas
Lauché, Constanza Elena
Muñoz, Luciana
Berengeno, Andrea Lorena
Colonna, Mariana
Ortega, Hugo Hector
Goldbaum, Fernando Alberto
Sanguineti, Santiago
Zylberman, Vanesa
author Hiriart, Yanina
author_facet Hiriart, Yanina
Pardo, Romina Paola
Bukata, Lucas
Lauché, Constanza Elena
Muñoz, Luciana
Berengeno, Andrea Lorena
Colonna, Mariana
Ortega, Hugo Hector
Goldbaum, Fernando Alberto
Sanguineti, Santiago
Zylberman, Vanesa
author_role author
author2 Pardo, Romina Paola
Bukata, Lucas
Lauché, Constanza Elena
Muñoz, Luciana
Berengeno, Andrea Lorena
Colonna, Mariana
Ortega, Hugo Hector
Goldbaum, Fernando Alberto
Sanguineti, Santiago
Zylberman, Vanesa
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Sindrome urémico hemolítico
tratamiento SUH
enfermedad renal
fragmentos F(ab')2
topic Sindrome urémico hemolítico
tratamiento SUH
enfermedad renal
fragmentos F(ab')2
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv STEC-HUS is a clinical syndrome characterized by the triad of thrombotic microangiopathy, thrombocytopenia and acute kidney injury. Despite the magnitude of the social and economic problems caused by STEC infections, there are currently no specific therapeutic options on the market. HUS is a toxemic disorder and the therapeutic effect of the early intervention with anti-toxin neutralizing antibodies has been supported in several animal models. We have designed novel protein nanoparticles with very strong immunogenic capacity by inserting Stx1B and Stx2B subunits of Shiga toxin to Brucella abortus Lumazine Synthase (BLS). The chimeric BLS-StxBs particles elicited strong neutralizing antibodies against Shiga toxins in horses. Based on these responses, we produced NEAST (Neutralizing Equine Anti-Shiga Toxin), composed of purified F(ab’)2 fragments. In this report we present the preclinical analysis of this new treatment. As a general conclusion, NEAST shows a very strong neutralizing capacity against 8 Shiga toxin variants in preclinical models of STEC-HUS. NEAST is also able to neutralize pathologic effects after previous exposure to Shiga Toxin, defining a potential therapeutic window. Besides, NEAST shows an excellent pharmacokinetics and safety profile in animal models. Overall, these results indicate that NEAST is a very good drug candidate for preventing the onset of HUS in STEC-infected patients and validate the conduction of a first in human clinical study at the Hospital Italiano de Buenos Aires in order to evaluate its safety and pharmacokinetic profiles in healthy adult volunteers.
Fil: Hiriart, Yanina. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Pardo, Romina Paola. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bukata, Lucas. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lauché, Constanza Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Muñoz, Luciana. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Berengeno, Andrea Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Colonna, Mariana. Inmunova S.A; Argentina
Fil: Ortega, Hugo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Goldbaum, Fernando Alberto. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Sanguineti, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina. Inmunova S.A; Argentina
Fil: Zylberman, Vanesa. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
description STEC-HUS is a clinical syndrome characterized by the triad of thrombotic microangiopathy, thrombocytopenia and acute kidney injury. Despite the magnitude of the social and economic problems caused by STEC infections, there are currently no specific therapeutic options on the market. HUS is a toxemic disorder and the therapeutic effect of the early intervention with anti-toxin neutralizing antibodies has been supported in several animal models. We have designed novel protein nanoparticles with very strong immunogenic capacity by inserting Stx1B and Stx2B subunits of Shiga toxin to Brucella abortus Lumazine Synthase (BLS). The chimeric BLS-StxBs particles elicited strong neutralizing antibodies against Shiga toxins in horses. Based on these responses, we produced NEAST (Neutralizing Equine Anti-Shiga Toxin), composed of purified F(ab’)2 fragments. In this report we present the preclinical analysis of this new treatment. As a general conclusion, NEAST shows a very strong neutralizing capacity against 8 Shiga toxin variants in preclinical models of STEC-HUS. NEAST is also able to neutralize pathologic effects after previous exposure to Shiga Toxin, defining a potential therapeutic window. Besides, NEAST shows an excellent pharmacokinetics and safety profile in animal models. Overall, these results indicate that NEAST is a very good drug candidate for preventing the onset of HUS in STEC-infected patients and validate the conduction of a first in human clinical study at the Hospital Italiano de Buenos Aires in order to evaluate its safety and pharmacokinetic profiles in healthy adult volunteers.
publishDate 2019
dc.date.none.fl_str_mv 2019-09
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/11336/174746
Hiriart, Yanina; Pardo, Romina Paola; Bukata, Lucas; Lauché, Constanza Elena; Muñoz, Luciana; et al.; Preclinical Studies of NEAST (Neutralizing Equine Anti-Shiga Toxin): A Potential Treatment for Prevention of Stec-Hus; Insight Medical Publishing; International Journal of Drug Development and Research; 11; 3; 9-2019; 15-24
CONICET Digital
CONICET
url http://hdl.handle.net/11336/174746
identifier_str_mv Hiriart, Yanina; Pardo, Romina Paola; Bukata, Lucas; Lauché, Constanza Elena; Muñoz, Luciana; et al.; Preclinical Studies of NEAST (Neutralizing Equine Anti-Shiga Toxin): A Potential Treatment for Prevention of Stec-Hus; Insight Medical Publishing; International Journal of Drug Development and Research; 11; 3; 9-2019; 15-24
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.ijddr.in/drug-development/preclinicalstudies-of-neast-neutralizing-equine-antishiga-to-xin-apotential-treatment-for-prevention-of-stechus.php?aid=24641
info:eu-repo/semantics/altIdentifier/doi/10.36648/0975-9344.11.3.140
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 Insight Medical Publishing
publisher.none.fl_str_mv Insight Medical Publishing
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 12.982451

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