Optimized adenoviral vector that enhances the assembly of FMDV O1 virus-like particles in situ increases its potential as vaccine for serotype O viruses
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 th...
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| Format: | info:ar-repo/semantics/artículo |
| Language: | Inglés |
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Frontiers Media
2021
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| Online Access: | 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 |
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| author | Ziraldo, Micaela Bidart, Juan Esteban Prato, Cecilia A. Tribulatti, María Virginia Zamorano, Patricia Ines Mattion, Nora Marta D’Antuono, Alejandra |
| author_browse | Bidart, Juan Esteban D’Antuono, Alejandra Mattion, Nora Marta Prato, Cecilia A. Tribulatti, María Virginia Zamorano, Patricia Ines 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_sort | Ziraldo, Micaela |
| collection | INTA Digital |
| 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. |
| format | info:ar-repo/semantics/artículo |
| id | INTA8586 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | Frontiers Media |
| publisherStr | Frontiers Media |
| record_format | dspace |
| spelling | INTA85862021-01-08T17:28:17Z 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 Bidart, Juan Esteban Prato, Cecilia A. Tribulatti, María Virginia Zamorano, Patricia Ines Mattion, Nora Marta D’Antuono, Alejandra Foot and Mouth Disease Aphthovirus Synthetic Vaccines Antibodies Viruses Fiebre Aftosa Virus Fiebre Aftosa Vacuna Sintética Anticuerpos Virus Adenoviral Vector Vector Adenoviral 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 2021-01-08T17:19:11Z 2021-01-08T17:19:11Z 2020-11 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 eng 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) application/pdf Frontiers Media Frontiers in Microbiology 11 : 591019 (Noviembre 2020) |
| spellingShingle | Foot and Mouth Disease Aphthovirus Synthetic Vaccines Antibodies Viruses Fiebre Aftosa Virus Fiebre Aftosa Vacuna Sintética Anticuerpos Virus Adenoviral Vector Vector Adenoviral Ziraldo, Micaela Bidart, Juan Esteban Prato, Cecilia A. Tribulatti, María Virginia Zamorano, Patricia Ines Mattion, Nora Marta D’Antuono, Alejandra 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 |
| 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_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_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 |
| topic | Foot and Mouth Disease Aphthovirus Synthetic Vaccines Antibodies Viruses Fiebre Aftosa Virus Fiebre Aftosa Vacuna Sintética Anticuerpos Virus Adenoviral Vector Vector Adenoviral |
| 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 |
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