Foot-and-Mouth Disease: Optimization, Reproducibility, and Scalability of High-Yield Production of Virus-Like Particles for a Next-Generation Vaccine
Inactivated Foot-and-Mouth Disease (FMD) vaccine has proven to be effective in the control of the disease. However, its production has some disadvantages, including the costly biosafety facilities required for the production of huge amounts of growing live virus, the need of an exhaustive purification process to eliminate non-structural proteins of the virus in the final formulations in order to differentiate infected from vaccinated animals and variable local regulatory restrictions to produce and commercialize the vaccine. Thus, a novel vaccine against FMD that overcome these restrictions is desirable. Although many developments have been made in this regard, most of them failed in terms of efficacy or when considering their transferability to the industry. We have previously reported the use of transient gene expression in mammalian cells to produce FMD virus-like particles (VLPs) as a novel vaccine for FMD and demonstrated the immunogenicity of the recombinant structures in animal models. Here, we report the optimization of the production system by assaying different DNA:polyethylenimine concentrations, cell densities, and direct and indirect protocols of transfection. Also, we evaluated the reproducibility and scalability of the technology to produce high yields of recombinant VLPs in a cost-effective and scalable system compatible with industrial tech-transfer of an effective and safe vaccine.
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Frontiers Media S.A.
2020-09
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Subjects: | Vacuna Inactivada, Fiebre Aftosa, Enfermedades de los Animales, Inactivated Vaccines, Foot and Mouth Disease, Animal Diseases, |
Online Access: | http://hdl.handle.net/20.500.12123/8502 https://www.frontiersin.org/articles/10.3389/fvets.2020.00601/full https://doi.org/10.3389/fvets.2020.00601 |
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oai:localhost:20.500.12123-85022020-12-28T16:58:36Z Foot-and-Mouth Disease: Optimization, Reproducibility, and Scalability of High-Yield Production of Virus-Like Particles for a Next-Generation Vaccine Mignaqui, Ana Clara Ferella, Alejandra Cass, Brian Mukankurayija, Larissa L’Abbé, Denis Bisson, Louis Sánchez, Cintia Scian, Romina Cardillo, Sabrina Beatriz Durocher, Yves Wigdorovitz, Andres Vacuna Inactivada Fiebre Aftosa Enfermedades de los Animales Inactivated Vaccines Foot and Mouth Disease Animal Diseases Inactivated Foot-and-Mouth Disease (FMD) vaccine has proven to be effective in the control of the disease. However, its production has some disadvantages, including the costly biosafety facilities required for the production of huge amounts of growing live virus, the need of an exhaustive purification process to eliminate non-structural proteins of the virus in the final formulations in order to differentiate infected from vaccinated animals and variable local regulatory restrictions to produce and commercialize the vaccine. Thus, a novel vaccine against FMD that overcome these restrictions is desirable. Although many developments have been made in this regard, most of them failed in terms of efficacy or when considering their transferability to the industry. We have previously reported the use of transient gene expression in mammalian cells to produce FMD virus-like particles (VLPs) as a novel vaccine for FMD and demonstrated the immunogenicity of the recombinant structures in animal models. Here, we report the optimization of the production system by assaying different DNA:polyethylenimine concentrations, cell densities, and direct and indirect protocols of transfection. Also, we evaluated the reproducibility and scalability of the technology to produce high yields of recombinant VLPs in a cost-effective and scalable system compatible with industrial tech-transfer of an effective and safe vaccine. Estación Experimental Agropecuaria Bariloche Fil: Mignaqui, Ana Clara. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Investigaciones Forestales y Agropecuarias Bariloche; Argentina Fil: Ferella, Alejandra. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina Fil: Cass, Brian. Human Health Therapeutics Research Center, National Research Council Canada; Canadá Fil Mukankurayija, Larissa. Human Health Therapeutics Research Center, National Research Council Canada; Canadá Fil: L’Abbé, Denis. Human Health Therapeutics Research Center, National Research Council Canada; Canadá Fil: Bisson, Louis. Human Health Therapeutics Research Center, National Research Council Canada; Canada Fil: Sánchez, Cintia. Biogénesis-Bagó; Argentina Fil: Scian, Romina. Biogénesis-Bagó; Argentina Fil: Cardillo, Sabrina Beatriz. Biogénesis-Bagó; Argentina Fil: Durocher, Yves. Human Health Therapeutics Research Center, National Research Council Canada; Canadá Fil: Wigdorovitz, Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina 2020-12-28T16:45:30Z 2020-12-28T16:45:30Z 2020-09 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/8502 https://www.frontiersin.org/articles/10.3389/fvets.2020.00601/full 2297-1769 https://doi.org/10.3389/fvets.2020.00601 eng info:eu-repo/semantics/openAccess application/pdf Frontiers Media S.A. Frontiers in Veterinary Science 7 : art. 601 (2020) |
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Vacuna Inactivada Fiebre Aftosa Enfermedades de los Animales Inactivated Vaccines Foot and Mouth Disease Animal Diseases Vacuna Inactivada Fiebre Aftosa Enfermedades de los Animales Inactivated Vaccines Foot and Mouth Disease Animal Diseases |
spellingShingle |
Vacuna Inactivada Fiebre Aftosa Enfermedades de los Animales Inactivated Vaccines Foot and Mouth Disease Animal Diseases Vacuna Inactivada Fiebre Aftosa Enfermedades de los Animales Inactivated Vaccines Foot and Mouth Disease Animal Diseases Mignaqui, Ana Clara Ferella, Alejandra Cass, Brian Mukankurayija, Larissa L’Abbé, Denis Bisson, Louis Sánchez, Cintia Scian, Romina Cardillo, Sabrina Beatriz Durocher, Yves Wigdorovitz, Andres Foot-and-Mouth Disease: Optimization, Reproducibility, and Scalability of High-Yield Production of Virus-Like Particles for a Next-Generation Vaccine |
description |
Inactivated Foot-and-Mouth Disease (FMD) vaccine has proven to be effective in the control of the disease. However, its production has some disadvantages, including the costly biosafety facilities required for the production of huge amounts of growing live virus,
the need of an exhaustive purification process to eliminate non-structural proteins of the virus in the final formulations in order to differentiate infected from vaccinated animals and variable local regulatory restrictions to produce and commercialize the vaccine. Thus, a novel vaccine against FMD that overcome these restrictions is desirable. Although many developments have been made in this regard, most of them failed in terms of efficacy or when considering their transferability to the industry. We have previously reported
the use of transient gene expression in mammalian cells to produce FMD virus-like particles (VLPs) as a novel vaccine for FMD and demonstrated the immunogenicity of the recombinant structures in animal models. Here, we report the optimization of the production system by assaying different DNA:polyethylenimine concentrations, cell densities, and direct and indirect protocols of transfection. Also, we evaluated the reproducibility and scalability of the technology to produce high yields of recombinant VLPs in a cost-effective and scalable system compatible with industrial tech-transfer of an effective and safe vaccine. |
format |
info:ar-repo/semantics/artículo |
topic_facet |
Vacuna Inactivada Fiebre Aftosa Enfermedades de los Animales Inactivated Vaccines Foot and Mouth Disease Animal Diseases |
author |
Mignaqui, Ana Clara Ferella, Alejandra Cass, Brian Mukankurayija, Larissa L’Abbé, Denis Bisson, Louis Sánchez, Cintia Scian, Romina Cardillo, Sabrina Beatriz Durocher, Yves Wigdorovitz, Andres |
author_facet |
Mignaqui, Ana Clara Ferella, Alejandra Cass, Brian Mukankurayija, Larissa L’Abbé, Denis Bisson, Louis Sánchez, Cintia Scian, Romina Cardillo, Sabrina Beatriz Durocher, Yves Wigdorovitz, Andres |
author_sort |
Mignaqui, Ana Clara |
title |
Foot-and-Mouth Disease: Optimization, Reproducibility, and Scalability of High-Yield Production of Virus-Like Particles for a Next-Generation Vaccine |
title_short |
Foot-and-Mouth Disease: Optimization, Reproducibility, and Scalability of High-Yield Production of Virus-Like Particles for a Next-Generation Vaccine |
title_full |
Foot-and-Mouth Disease: Optimization, Reproducibility, and Scalability of High-Yield Production of Virus-Like Particles for a Next-Generation Vaccine |
title_fullStr |
Foot-and-Mouth Disease: Optimization, Reproducibility, and Scalability of High-Yield Production of Virus-Like Particles for a Next-Generation Vaccine |
title_full_unstemmed |
Foot-and-Mouth Disease: Optimization, Reproducibility, and Scalability of High-Yield Production of Virus-Like Particles for a Next-Generation Vaccine |
title_sort |
foot-and-mouth disease: optimization, reproducibility, and scalability of high-yield production of virus-like particles for a next-generation vaccine |
publisher |
Frontiers Media S.A. |
publishDate |
2020-09 |
url |
http://hdl.handle.net/20.500.12123/8502 https://www.frontiersin.org/articles/10.3389/fvets.2020.00601/full https://doi.org/10.3389/fvets.2020.00601 |
work_keys_str_mv |
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