Optimized adenoviral vector that enhances the assembly of FMDV O1 virus-like particles in situ increases its potential as vaccine for serotype O viruses

Autores
Ziraldo, Micaela; Bidart, Juan Esteban; Prato, Cecilia Arahi; Tribulatti, Maria Virginia; Zamorano, Patricia Ines; Mattion, Nora Marta; D'antuono, Alejandra Lorena
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Although replication-defective human adenovirus type 5 (Ad5) vectors that express in situ the capsid-encoding regions of Foot-and-mouth disease virus (FMDV) have proved to be effective as vaccines in relevant species for several viral strains, the same result was not achieved for O1/Campos/Brazil/58 strain. In the present study, an optimization of the Ad5 system was explored and proved to enhance the level of capsid proteins expression and favor their association into virus-like particles (VLPs). Particularly, we engineered a novel Ad5 vector (Ad5[PVP2]OP) carrying the FMDV sequences under the control of an optimized CMV promoter and inserted in an opposite transcriptional orientation relative to the Ad5 genome. The Ad5[PVP2]OP vaccine candidate also contains the amino acid substitutions S93F/Y98F in the VP2 protein-coding sequence, predicted to stabilize FMD virus particles. Cells infected with the optimized vector showed a 14-fold increase in protein expression as compared to cells infected with an unmodified Ad5 vector tested in previous works. Furthermore, amino acid substitutions in VP2 protein allowed the assembly of FMDV O1/Campos/Brazil/58 VLPs. Evaluation of several serological parameters in inoculated mice with Ad5[PVP2]OP revealed an enhanced vaccine performance, as compare to the unmodified Ad5 vector, in terms of statistically significant higher titers of neutralizing antibodies, being similar to mice inoculated with the inactivated adjuvanted vaccine. Moreover, 94% of mice vaccinated with Ad5[PVP2]OP candidate were protected from homologous challenge. These results indicate that both the optimized protein expression and the stabilization of the in situ generated VLPs improved the performance of Ad5-vectored vaccines against FMDV O1/Campos/Brazil/58 strain, and open optimistic expectations to be tested in target animals.
Fil: Ziraldo, Micaela. Ministerio de Producción y Trabajo. Secretaría de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virología Humana y Animal. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Virología Humana y Animal; Argentina
Fil: Bidart, Juan Esteban. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas.; Argentina
Fil: Prato, Cecilia Arahi. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Tribulatti, Maria Virginia. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Zamorano, Patricia Ines. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas.; Argentina; Argentina
Fil: Mattion, Nora Marta. Ministerio de Producción y Trabajo. Secretaría de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virología Humana y Animal. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Virología Humana y Animal; Argentina
Fil: D'antuono, Alejandra Lorena. Ministerio de Producción y Trabajo. Secretaría de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virología Humana y Animal. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Virología Humana y Animal; Argentina
Materia
FOOT-AND-MOUTH DISEASE VIRUS
ADENOVIRUS TYPE 5 REPLICATION-DEFICIENT
VIRUS LIKE PARTICLES
GENETIC 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:11336/167722
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/167722
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Optimized adenoviral vector that enhances the assembly of FMDV O1 virus-like particles in situ increases its potential as vaccine for serotype O virusesZiraldo, MicaelaBidart, Juan EstebanPrato, Cecilia ArahiTribulatti, Maria VirginiaZamorano, Patricia InesMattion, Nora MartaD'antuono, Alejandra LorenaFOOT-AND-MOUTH DISEASE VIRUSADENOVIRUS TYPE 5 REPLICATION-DEFICIENTVIRUS LIKE PARTICLESGENETIC VACCINEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Although replication-defective human adenovirus type 5 (Ad5) vectors that express in situ the capsid-encoding regions of Foot-and-mouth disease virus (FMDV) have proved to be effective as vaccines in relevant species for several viral strains, the same result was not achieved for O1/Campos/Brazil/58 strain. In the present study, an optimization of the Ad5 system was explored and proved to enhance the level of capsid proteins expression and favor their association into virus-like particles (VLPs). Particularly, we engineered a novel Ad5 vector (Ad5[PVP2]OP) carrying the FMDV sequences under the control of an optimized CMV promoter and inserted in an opposite transcriptional orientation relative to the Ad5 genome. The Ad5[PVP2]OP vaccine candidate also contains the amino acid substitutions S93F/Y98F in the VP2 protein-coding sequence, predicted to stabilize FMD virus particles. Cells infected with the optimized vector showed a 14-fold increase in protein expression as compared to cells infected with an unmodified Ad5 vector tested in previous works. Furthermore, amino acid substitutions in VP2 protein allowed the assembly of FMDV O1/Campos/Brazil/58 VLPs. Evaluation of several serological parameters in inoculated mice with Ad5[PVP2]OP revealed an enhanced vaccine performance, as compare to the unmodified Ad5 vector, in terms of statistically significant higher titers of neutralizing antibodies, being similar to mice inoculated with the inactivated adjuvanted vaccine. Moreover, 94% of mice vaccinated with Ad5[PVP2]OP candidate were protected from homologous challenge. These results indicate that both the optimized protein expression and the stabilization of the in situ generated VLPs improved the performance of Ad5-vectored vaccines against FMDV O1/Campos/Brazil/58 strain, and open optimistic expectations to be tested in target animals.Fil: Ziraldo, Micaela. Ministerio de Producción y Trabajo. Secretaría de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virología Humana y Animal. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Virología Humana y Animal; ArgentinaFil: Bidart, Juan Esteban. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas.; ArgentinaFil: Prato, Cecilia Arahi. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Tribulatti, Maria Virginia. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Zamorano, Patricia Ines. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas.; Argentina; ArgentinaFil: Mattion, Nora Marta. Ministerio de Producción y Trabajo. Secretaría de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virología Humana y Animal. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Virología Humana y Animal; ArgentinaFil: D'antuono, Alejandra Lorena. Ministerio de Producción y Trabajo. Secretaría de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virología Humana y Animal. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Virología Humana y Animal; ArgentinaFrontiers Media2020-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/167722Ziraldo, Micaela; Bidart, Juan Esteban; Prato, Cecilia Arahi; Tribulatti, Maria Virginia; Zamorano, Patricia Ines; et al.; Optimized adenoviral vector that enhances the assembly of FMDV O1 virus-like particles in situ increases its potential as vaccine for serotype O viruses; Frontiers Media; Frontiers in Microbiology; 11; 591019; 9-2020; 191664-302XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.frontiersin.org/Review/EnterReviewForum.aspx?activationno=eb31c2a5-c6ea-4cca-8bee-975fbca43f1ainfo:eu-repo/semantics/altIdentifier/doi/10.3389/fmicb.2020.591019info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:31:12Zoai:ri.conicet.gov.ar:11336/167722instacron: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 11:31:13.056CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Optimized adenoviral vector that enhances the assembly of FMDV O1 virus-like particles in situ increases its potential as vaccine for serotype O viruses
title Optimized adenoviral vector that enhances the assembly of FMDV O1 virus-like particles in situ increases its potential as vaccine for serotype O viruses
spellingShingle Optimized adenoviral vector that enhances the assembly of FMDV O1 virus-like particles in situ increases its potential as vaccine for serotype O viruses
Ziraldo, Micaela
FOOT-AND-MOUTH DISEASE VIRUS
ADENOVIRUS TYPE 5 REPLICATION-DEFICIENT
VIRUS LIKE PARTICLES
GENETIC VACCINE
title_short Optimized adenoviral vector that enhances the assembly of FMDV O1 virus-like particles in situ increases its potential as vaccine for serotype O viruses
title_full Optimized adenoviral vector that enhances the assembly of FMDV O1 virus-like particles in situ increases its potential as vaccine for serotype O viruses
title_fullStr Optimized adenoviral vector that enhances the assembly of FMDV O1 virus-like particles in situ increases its potential as vaccine for serotype O viruses
title_full_unstemmed Optimized adenoviral vector that enhances the assembly of FMDV O1 virus-like particles in situ increases its potential as vaccine for serotype O viruses
title_sort Optimized adenoviral vector that enhances the assembly of FMDV O1 virus-like particles in situ increases its potential as vaccine for serotype O viruses
dc.creator.none.fl_str_mv Ziraldo, Micaela
Bidart, Juan Esteban
Prato, Cecilia Arahi
Tribulatti, Maria Virginia
Zamorano, Patricia Ines
Mattion, Nora Marta
D'antuono, Alejandra Lorena
author Ziraldo, Micaela
author_facet Ziraldo, Micaela
Bidart, Juan Esteban
Prato, Cecilia Arahi
Tribulatti, Maria Virginia
Zamorano, Patricia Ines
Mattion, Nora Marta
D'antuono, Alejandra Lorena
author_role author
author2 Bidart, Juan Esteban
Prato, Cecilia Arahi
Tribulatti, Maria Virginia
Zamorano, Patricia Ines
Mattion, Nora Marta
D'antuono, Alejandra Lorena
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv FOOT-AND-MOUTH DISEASE VIRUS
ADENOVIRUS TYPE 5 REPLICATION-DEFICIENT
VIRUS LIKE PARTICLES
GENETIC VACCINE
topic FOOT-AND-MOUTH DISEASE VIRUS
ADENOVIRUS TYPE 5 REPLICATION-DEFICIENT
VIRUS LIKE PARTICLES
GENETIC 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 Although replication-defective human adenovirus type 5 (Ad5) vectors that express in situ the capsid-encoding regions of Foot-and-mouth disease virus (FMDV) have proved to be effective as vaccines in relevant species for several viral strains, the same result was not achieved for O1/Campos/Brazil/58 strain. In the present study, an optimization of the Ad5 system was explored and proved to enhance the level of capsid proteins expression and favor their association into virus-like particles (VLPs). Particularly, we engineered a novel Ad5 vector (Ad5[PVP2]OP) carrying the FMDV sequences under the control of an optimized CMV promoter and inserted in an opposite transcriptional orientation relative to the Ad5 genome. The Ad5[PVP2]OP vaccine candidate also contains the amino acid substitutions S93F/Y98F in the VP2 protein-coding sequence, predicted to stabilize FMD virus particles. Cells infected with the optimized vector showed a 14-fold increase in protein expression as compared to cells infected with an unmodified Ad5 vector tested in previous works. Furthermore, amino acid substitutions in VP2 protein allowed the assembly of FMDV O1/Campos/Brazil/58 VLPs. Evaluation of several serological parameters in inoculated mice with Ad5[PVP2]OP revealed an enhanced vaccine performance, as compare to the unmodified Ad5 vector, in terms of statistically significant higher titers of neutralizing antibodies, being similar to mice inoculated with the inactivated adjuvanted vaccine. Moreover, 94% of mice vaccinated with Ad5[PVP2]OP candidate were protected from homologous challenge. These results indicate that both the optimized protein expression and the stabilization of the in situ generated VLPs improved the performance of Ad5-vectored vaccines against FMDV O1/Campos/Brazil/58 strain, and open optimistic expectations to be tested in target animals.
Fil: Ziraldo, Micaela. Ministerio de Producción y Trabajo. Secretaría de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virología Humana y Animal. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Virología Humana y Animal; Argentina
Fil: Bidart, Juan Esteban. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas.; Argentina
Fil: Prato, Cecilia Arahi. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Tribulatti, Maria Virginia. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Zamorano, Patricia Ines. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas.; Argentina; Argentina
Fil: Mattion, Nora Marta. Ministerio de Producción y Trabajo. Secretaría de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virología Humana y Animal. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Virología Humana y Animal; Argentina
Fil: D'antuono, Alejandra Lorena. Ministerio de Producción y Trabajo. Secretaría de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virología Humana y Animal. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Virología Humana y Animal; Argentina
description Although replication-defective human adenovirus type 5 (Ad5) vectors that express in situ the capsid-encoding regions of Foot-and-mouth disease virus (FMDV) have proved to be effective as vaccines in relevant species for several viral strains, the same result was not achieved for O1/Campos/Brazil/58 strain. In the present study, an optimization of the Ad5 system was explored and proved to enhance the level of capsid proteins expression and favor their association into virus-like particles (VLPs). Particularly, we engineered a novel Ad5 vector (Ad5[PVP2]OP) carrying the FMDV sequences under the control of an optimized CMV promoter and inserted in an opposite transcriptional orientation relative to the Ad5 genome. The Ad5[PVP2]OP vaccine candidate also contains the amino acid substitutions S93F/Y98F in the VP2 protein-coding sequence, predicted to stabilize FMD virus particles. Cells infected with the optimized vector showed a 14-fold increase in protein expression as compared to cells infected with an unmodified Ad5 vector tested in previous works. Furthermore, amino acid substitutions in VP2 protein allowed the assembly of FMDV O1/Campos/Brazil/58 VLPs. Evaluation of several serological parameters in inoculated mice with Ad5[PVP2]OP revealed an enhanced vaccine performance, as compare to the unmodified Ad5 vector, in terms of statistically significant higher titers of neutralizing antibodies, being similar to mice inoculated with the inactivated adjuvanted vaccine. Moreover, 94% of mice vaccinated with Ad5[PVP2]OP candidate were protected from homologous challenge. These results indicate that both the optimized protein expression and the stabilization of the in situ generated VLPs improved the performance of Ad5-vectored vaccines against FMDV O1/Campos/Brazil/58 strain, and open optimistic expectations to be tested in target animals.
publishDate 2020
dc.date.none.fl_str_mv 2020-09
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/11336/167722
Ziraldo, Micaela; Bidart, Juan Esteban; Prato, Cecilia Arahi; Tribulatti, Maria Virginia; Zamorano, Patricia Ines; et al.; Optimized adenoviral vector that enhances the assembly of FMDV O1 virus-like particles in situ increases its potential as vaccine for serotype O viruses; Frontiers Media; Frontiers in Microbiology; 11; 591019; 9-2020; 19
1664-302X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/167722
identifier_str_mv Ziraldo, Micaela; Bidart, Juan Esteban; Prato, Cecilia Arahi; Tribulatti, Maria Virginia; Zamorano, Patricia Ines; et al.; Optimized adenoviral vector that enhances the assembly of FMDV O1 virus-like particles in situ increases its potential as vaccine for serotype O viruses; Frontiers Media; Frontiers in Microbiology; 11; 591019; 9-2020; 19
1664-302X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.3389/fmicb.2020.591019
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 Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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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