Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability
- Autores
- Mufarrege, Eduardo Federico; Peña, Lucía Carolina; Etcheverrigaray, Marina; De Groot, Anne S.; Martin, William
- Año de publicación
- 2023
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- For decades, recombinant human interferon alpha (rhIFN-α2b) has been used to treat emerging and chronic viral diseases. However, rhIFN-α2b is immunogenic and has a short in vivo half-life. To solve these limitations, two long-lasting hyperglycosylated proteins with reduced immunogenicity were developed and designated as 4N-IFN(VAR1) and 4N-IFN(VAR3). Here, we continue to study the relevant characteristics of these therapeutic candidates. Thus, we demonstrated that both de-immunized IFN versions elicited significantly lower neutralizing antibody responses than the original molecule in HLA-DR1 transgenic mice, confirming our previous in vitro protein immunogenicity data. Also, we found that these biobetters exhibited remarkable stability when exposed to different physical factors that the protein product may encounter during its production process and storage, such as low pH, thermal stress, and repeated freezing/thawing cycles. Taking into consideration our previous and present results, 4N-IFN(VAR1) and 4N-IFN-4N(VAR3) appear to be valuable candidates for the treatment of human viral diseases.
Fil: Mufarrege, Eduardo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina
Fil: Peña, Lucía Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina
Fil: Etcheverrigaray, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina
Fil: De Groot, Anne S.. Epivax Inc.; Estados Unidos. University Of Rhode Island; Estados Unidos
Fil: Martin, William. Epivax Inc.; Estados Unidos - Materia
-
ANTI-VIRAL THERAPY
DE-IMMUNIZATION
EPIMATRIX
IFN ALPHA
IMMUNOGENICITY
IN VIVO ASSAYS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/222810
Ver los metadatos del registro completo
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CONICET Digital (CONICET) |
spelling |
Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stabilityMufarrege, Eduardo FedericoPeña, Lucía CarolinaEtcheverrigaray, MarinaDe Groot, Anne S.Martin, WilliamANTI-VIRAL THERAPYDE-IMMUNIZATIONEPIMATRIXIFN ALPHAIMMUNOGENICITYIN VIVO ASSAYShttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3For decades, recombinant human interferon alpha (rhIFN-α2b) has been used to treat emerging and chronic viral diseases. However, rhIFN-α2b is immunogenic and has a short in vivo half-life. To solve these limitations, two long-lasting hyperglycosylated proteins with reduced immunogenicity were developed and designated as 4N-IFN(VAR1) and 4N-IFN(VAR3). Here, we continue to study the relevant characteristics of these therapeutic candidates. Thus, we demonstrated that both de-immunized IFN versions elicited significantly lower neutralizing antibody responses than the original molecule in HLA-DR1 transgenic mice, confirming our previous in vitro protein immunogenicity data. Also, we found that these biobetters exhibited remarkable stability when exposed to different physical factors that the protein product may encounter during its production process and storage, such as low pH, thermal stress, and repeated freezing/thawing cycles. Taking into consideration our previous and present results, 4N-IFN(VAR1) and 4N-IFN-4N(VAR3) appear to be valuable candidates for the treatment of human viral diseases.Fil: Mufarrege, Eduardo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; ArgentinaFil: Peña, Lucía Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; ArgentinaFil: Etcheverrigaray, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; ArgentinaFil: De Groot, Anne S.. Epivax Inc.; Estados Unidos. University Of Rhode Island; Estados UnidosFil: Martin, William. Epivax Inc.; Estados UnidosElsevier2023-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/222810Mufarrege, Eduardo Federico; Peña, Lucía Carolina; Etcheverrigaray, Marina; De Groot, Anne S.; Martin, William; Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability; Elsevier; Heliyon; 9; 3; 3-2023; 1-102405-8440CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2405844023018777info:eu-repo/semantics/altIdentifier/doi/10.1016/j.heliyon.2023.e14670info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:29:10Zoai:ri.conicet.gov.ar:11336/222810instacron: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 10:29:11.21CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability |
title |
Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability |
spellingShingle |
Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability Mufarrege, Eduardo Federico ANTI-VIRAL THERAPY DE-IMMUNIZATION EPIMATRIX IFN ALPHA IMMUNOGENICITY IN VIVO ASSAYS |
title_short |
Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability |
title_full |
Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability |
title_fullStr |
Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability |
title_full_unstemmed |
Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability |
title_sort |
Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability |
dc.creator.none.fl_str_mv |
Mufarrege, Eduardo Federico Peña, Lucía Carolina Etcheverrigaray, Marina De Groot, Anne S. Martin, William |
author |
Mufarrege, Eduardo Federico |
author_facet |
Mufarrege, Eduardo Federico Peña, Lucía Carolina Etcheverrigaray, Marina De Groot, Anne S. Martin, William |
author_role |
author |
author2 |
Peña, Lucía Carolina Etcheverrigaray, Marina De Groot, Anne S. Martin, William |
author2_role |
author author author author |
dc.subject.none.fl_str_mv |
ANTI-VIRAL THERAPY DE-IMMUNIZATION EPIMATRIX IFN ALPHA IMMUNOGENICITY IN VIVO ASSAYS |
topic |
ANTI-VIRAL THERAPY DE-IMMUNIZATION EPIMATRIX IFN ALPHA IMMUNOGENICITY IN VIVO ASSAYS |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.4 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
For decades, recombinant human interferon alpha (rhIFN-α2b) has been used to treat emerging and chronic viral diseases. However, rhIFN-α2b is immunogenic and has a short in vivo half-life. To solve these limitations, two long-lasting hyperglycosylated proteins with reduced immunogenicity were developed and designated as 4N-IFN(VAR1) and 4N-IFN(VAR3). Here, we continue to study the relevant characteristics of these therapeutic candidates. Thus, we demonstrated that both de-immunized IFN versions elicited significantly lower neutralizing antibody responses than the original molecule in HLA-DR1 transgenic mice, confirming our previous in vitro protein immunogenicity data. Also, we found that these biobetters exhibited remarkable stability when exposed to different physical factors that the protein product may encounter during its production process and storage, such as low pH, thermal stress, and repeated freezing/thawing cycles. Taking into consideration our previous and present results, 4N-IFN(VAR1) and 4N-IFN-4N(VAR3) appear to be valuable candidates for the treatment of human viral diseases. Fil: Mufarrege, Eduardo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina Fil: Peña, Lucía Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina Fil: Etcheverrigaray, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina Fil: De Groot, Anne S.. Epivax Inc.; Estados Unidos. University Of Rhode Island; Estados Unidos Fil: Martin, William. Epivax Inc.; Estados Unidos |
description |
For decades, recombinant human interferon alpha (rhIFN-α2b) has been used to treat emerging and chronic viral diseases. However, rhIFN-α2b is immunogenic and has a short in vivo half-life. To solve these limitations, two long-lasting hyperglycosylated proteins with reduced immunogenicity were developed and designated as 4N-IFN(VAR1) and 4N-IFN(VAR3). Here, we continue to study the relevant characteristics of these therapeutic candidates. Thus, we demonstrated that both de-immunized IFN versions elicited significantly lower neutralizing antibody responses than the original molecule in HLA-DR1 transgenic mice, confirming our previous in vitro protein immunogenicity data. Also, we found that these biobetters exhibited remarkable stability when exposed to different physical factors that the protein product may encounter during its production process and storage, such as low pH, thermal stress, and repeated freezing/thawing cycles. Taking into consideration our previous and present results, 4N-IFN(VAR1) and 4N-IFN-4N(VAR3) appear to be valuable candidates for the treatment of human viral diseases. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-03 |
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/11336/222810 Mufarrege, Eduardo Federico; Peña, Lucía Carolina; Etcheverrigaray, Marina; De Groot, Anne S.; Martin, William; Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability; Elsevier; Heliyon; 9; 3; 3-2023; 1-10 2405-8440 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/222810 |
identifier_str_mv |
Mufarrege, Eduardo Federico; Peña, Lucía Carolina; Etcheverrigaray, Marina; De Groot, Anne S.; Martin, William; Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability; Elsevier; Heliyon; 9; 3; 3-2023; 1-10 2405-8440 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2405844023018777 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.heliyon.2023.e14670 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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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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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13.070432 |