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Expression and Purification of Virus-like Particles for Vaccination
Published on: June 2, 2016
Transiently Transfected Mammalian Cell Cultures: An Adaptable and Effective Platform for Virus-like Particle-Based
Michael Puckette1, Victoria Primavera2,3, Erica Martel4
1Plum Island Animal Disease Center, U.S. Department of Homeland Security Science and Technology Directorate, New York, NY 11944, USA.
Abstract:
RNA viruses, such as foot-and-mouth disease virus (FMDV), have error-prone replication resulting in the continuous emergence of new viral strains capable of evading current vaccine coverage. Vaccine formulations must be regularly updated, which is both costly and technically challenging for many vaccine platforms. In this report, we describe a plasmid-based virus-like particle (VLP) production platform utilizing transiently transfected mammalian cell cultures that combines both the rapid response adaptability of nucleic-acid-based vaccines with the ability to produce intact capsid epitopes required for immunity. Formulated vaccines which employed this platform conferred complete protection from clinical foot-and-mouth disease in both swine and cattle. This novel platform can be quickly adapted to new viral strains and serotypes through targeted exchanges of only the FMDV capsid polypeptide nucleic acid sequences, from which processed structural capsid proteins are derived. This platform obviates the need for high biocontainment manufacturing facilities to produce inactivated whole-virus vaccines from infected mammalian cell cultures, which requires upstream expansion and downstream concentration of large quantities of live virulent viruses.
Insights
A novel plasmid-based platform rapidly produces virus-like particles for foot-and-mouth disease virus (FMDV) vaccines. This adaptable technology offers complete protection in swine and cattle, overcoming challenges with traditional vaccine development.
Area of Science:
- Veterinary Virology
- Vaccine Technology
- Molecular Biology
Background:
- RNA viruses like foot-and-mouth disease virus (FMDV) evolve rapidly, necessitating frequent vaccine updates.
- Current vaccine production methods are costly and technically challenging, especially for rapidly mutating viruses.
- Existing platforms struggle to keep pace with viral strain emergence, impacting vaccine efficacy.
Purpose of the Study:
- To develop a rapid and adaptable vaccine production platform for FMDV.
- To create virus-like particles (VLPs) that elicit protective immunity against FMDV.
- To demonstrate the efficacy of VLP-based vaccines in target animal models.
Main Methods:
- Utilized a plasmid-based system for transient transfection of mammalian cell cultures.
- Engineered the platform for rapid adaptation by modifying FMDV capsid polypeptide nucleic acid sequences.
- Formulated vaccines using VLPs produced by the novel platform.
Main Results:
- The developed platform successfully produced intact capsid epitopes required for immunity.
- Vaccines formulated with VLPs conferred complete protection against clinical foot-and-mouth disease in swine and cattle.
- The platform demonstrated rapid adaptability to new viral strains and serotypes.
Conclusions:
- The plasmid-based VLP production platform offers a rapid response adaptable to emerging FMDV strains.
- This technology combines advantages of nucleic-acid-based vaccines with the need for intact capsid epitopes.
- The platform obviates the need for high biocontainment facilities for inactivated whole-virus vaccine production.
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