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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Main Authors: 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
Format: info:ar-repo/semantics/artículo biblioteca
Language:eng
Published: Frontiers Media S.A. 2020-09
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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spelling 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)
institution INTA AR
collection DSpace
country Argentina
countrycode AR
component Bibliográfico
access En linea
databasecode dig-inta-ar
tag biblioteca
region America del Sur
libraryname Biblioteca Central del INTA Argentina
language eng
topic 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
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