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 A.; Tribulatti, María Virginia; Zamorano, Patricia Ines; Mattion, Nora Marta; D’Antuono, Alejandra
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 region of foot-and-mouth disease virus (FMDV) have been proven to be effective as vaccines in relevant species for several viral strains, the same result was not consistently achieved for the O1/Campos/Brazil/58 strain. In the present study, an optimization of the Ad5 system was explored and was proven to enhance the expression of FMDV capsid proteins and their association into virus-like particles (VLPs). Particularly, we engineered a novel Ad5 vector (Ad5[PVP2]OP) which harbors the foreign transcription unit in a leftward orientation relative to the Ad5 genome, and drives the expression of the FMDV sequences from an optimized cytomegalovirus (CMV) enhancer-promoter as well. 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 an ∼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 the optimized Ad5[PVP2]OP candidate revealed an enhanced vaccine performance, characterized by significant higher titers of neutralizing antibodies, as compared to our previous unmodified Ad5 vector. Moreover, 94% of the mice vaccinated with the 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 the FMDV O1/Campos/Brazil/58 strain and open optimistic expectations to be tested in target animals.
Instituto de Virología
Fil: Ziraldo, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Virología Animal; Argentina
Fil: Bidart, Juan Esteban. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Prato, Cecilia A. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Laboratorio de Inmunología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Tribulatti, María Virginia. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Laboratorio de Inmunología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Zamorano, Patricia Ines. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mattion, Nora Marta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Virología Animal; Argentina
Fil: D'Antuono, Alejandra. Centro de Virología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fuente
Frontiers in Microbiology 11 : 591019 (Noviembre 2020)
Materia
Foot and Mouth Disease
Aphthovirus
Synthetic Vaccines
Antibodies
Viruses
Fiebre Aftosa
Virus Fiebre Aftosa
Vacuna Sintética
Anticuerpos
Virus
Adenoviral Vector
Vector Adenoviral
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/8586
Acceder
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oai_identifier_str oai:localhost:20.500.12123/8586
network_acronym_str INTADig
repository_id_str l
network_name_str INTA Digital (INTA)
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 A.Tribulatti, María VirginiaZamorano, Patricia InesMattion, Nora MartaD’Antuono, AlejandraFoot and Mouth DiseaseAphthovirusSynthetic VaccinesAntibodiesVirusesFiebre AftosaVirus Fiebre AftosaVacuna SintéticaAnticuerposVirusAdenoviral VectorVector AdenoviralAlthough replication-defective human adenovirus type 5 (Ad5) vectors that express in situ the capsid-encoding region of foot-and-mouth disease virus (FMDV) have been proven to be effective as vaccines in relevant species for several viral strains, the same result was not consistently achieved for the O1/Campos/Brazil/58 strain. In the present study, an optimization of the Ad5 system was explored and was proven to enhance the expression of FMDV capsid proteins and their association into virus-like particles (VLPs). Particularly, we engineered a novel Ad5 vector (Ad5[PVP2]OP) which harbors the foreign transcription unit in a leftward orientation relative to the Ad5 genome, and drives the expression of the FMDV sequences from an optimized cytomegalovirus (CMV) enhancer-promoter as well. 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 an ∼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 the optimized Ad5[PVP2]OP candidate revealed an enhanced vaccine performance, characterized by significant higher titers of neutralizing antibodies, as compared to our previous unmodified Ad5 vector. Moreover, 94% of the mice vaccinated with the 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 the FMDV O1/Campos/Brazil/58 strain and open optimistic expectations to be tested in target animals.Instituto de VirologíaFil: Ziraldo, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Virología Animal; ArgentinaFil: Bidart, Juan Esteban. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Prato, Cecilia A. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Laboratorio de Inmunología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tribulatti, María Virginia. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Laboratorio de Inmunología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zamorano, Patricia Ines. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mattion, Nora Marta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Virología Animal; ArgentinaFil: D'Antuono, Alejandra. Centro de Virología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFrontiers Media2021-01-08T17:19:11Z2021-01-08T17:19:11Z2020-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://www.frontiersin.org/articles/10.3389/fmicb.2020.591019/fullhttp://hdl.handle.net/20.500.12123/85861664-302Xhttps://doi.org/10.3389/fmicb.2020.591019Frontiers in Microbiology 11 : 591019 (Noviembre 2020)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-09-29T13:45:07Zoai:localhost:20.500.12123/8586instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-29 13:45:07.6INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
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
Aphthovirus
Synthetic Vaccines
Antibodies
Viruses
Fiebre Aftosa
Virus Fiebre Aftosa
Vacuna Sintética
Anticuerpos
Virus
Adenoviral Vector
Vector Adenoviral
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 A.
Tribulatti, María Virginia
Zamorano, Patricia Ines
Mattion, Nora Marta
D’Antuono, Alejandra
author Ziraldo, Micaela
author_facet Ziraldo, Micaela
Bidart, Juan Esteban
Prato, Cecilia A.
Tribulatti, María Virginia
Zamorano, Patricia Ines
Mattion, Nora Marta
D’Antuono, Alejandra
author_role author
author2 Bidart, Juan Esteban
Prato, Cecilia A.
Tribulatti, María Virginia
Zamorano, Patricia Ines
Mattion, Nora Marta
D’Antuono, Alejandra
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Foot and Mouth Disease
Aphthovirus
Synthetic Vaccines
Antibodies
Viruses
Fiebre Aftosa
Virus Fiebre Aftosa
Vacuna Sintética
Anticuerpos
Virus
Adenoviral Vector
Vector Adenoviral
topic Foot and Mouth Disease
Aphthovirus
Synthetic Vaccines
Antibodies
Viruses
Fiebre Aftosa
Virus Fiebre Aftosa
Vacuna Sintética
Anticuerpos
Virus
Adenoviral Vector
Vector Adenoviral
dc.description.none.fl_txt_mv Although replication-defective human adenovirus type 5 (Ad5) vectors that express in situ the capsid-encoding region of foot-and-mouth disease virus (FMDV) have been proven to be effective as vaccines in relevant species for several viral strains, the same result was not consistently achieved for the O1/Campos/Brazil/58 strain. In the present study, an optimization of the Ad5 system was explored and was proven to enhance the expression of FMDV capsid proteins and their association into virus-like particles (VLPs). Particularly, we engineered a novel Ad5 vector (Ad5[PVP2]OP) which harbors the foreign transcription unit in a leftward orientation relative to the Ad5 genome, and drives the expression of the FMDV sequences from an optimized cytomegalovirus (CMV) enhancer-promoter as well. 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 an ∼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 the optimized Ad5[PVP2]OP candidate revealed an enhanced vaccine performance, characterized by significant higher titers of neutralizing antibodies, as compared to our previous unmodified Ad5 vector. Moreover, 94% of the mice vaccinated with the 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 the FMDV O1/Campos/Brazil/58 strain and open optimistic expectations to be tested in target animals.
Instituto de Virología
Fil: Ziraldo, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Virología Animal; Argentina
Fil: Bidart, Juan Esteban. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Prato, Cecilia A. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Laboratorio de Inmunología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Tribulatti, María Virginia. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Laboratorio de Inmunología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Zamorano, Patricia Ines. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mattion, Nora Marta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Virología Animal; Argentina
Fil: D'Antuono, Alejandra. Centro de Virología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Although replication-defective human adenovirus type 5 (Ad5) vectors that express in situ the capsid-encoding region of foot-and-mouth disease virus (FMDV) have been proven to be effective as vaccines in relevant species for several viral strains, the same result was not consistently achieved for the O1/Campos/Brazil/58 strain. In the present study, an optimization of the Ad5 system was explored and was proven to enhance the expression of FMDV capsid proteins and their association into virus-like particles (VLPs). Particularly, we engineered a novel Ad5 vector (Ad5[PVP2]OP) which harbors the foreign transcription unit in a leftward orientation relative to the Ad5 genome, and drives the expression of the FMDV sequences from an optimized cytomegalovirus (CMV) enhancer-promoter as well. 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 an ∼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 the optimized Ad5[PVP2]OP candidate revealed an enhanced vaccine performance, characterized by significant higher titers of neutralizing antibodies, as compared to our previous unmodified Ad5 vector. Moreover, 94% of the mice vaccinated with the 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 the FMDV O1/Campos/Brazil/58 strain and open optimistic expectations to be tested in target animals.
publishDate 2020
dc.date.none.fl_str_mv 2020-11
2021-01-08T17:19:11Z
2021-01-08T17:19:11Z
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 https://www.frontiersin.org/articles/10.3389/fmicb.2020.591019/full
http://hdl.handle.net/20.500.12123/8586
1664-302X
https://doi.org/10.3389/fmicb.2020.591019
url https://www.frontiersin.org/articles/10.3389/fmicb.2020.591019/full
http://hdl.handle.net/20.500.12123/8586
https://doi.org/10.3389/fmicb.2020.591019
identifier_str_mv 1664-302X
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Frontiers in Microbiology 11 : 591019 (Noviembre 2020)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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