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Controlled vs. non-controlled culture systems for SARS-CoV-2 VLP production using the baculovirus/SF9 platform
Luis Giovani de Oliveira Guardalini1, Felipe Moura Dias1,2, Thaissa Consoni Bernardino1
1Laboratório de Biotecnologia Viral, Instituto Butantan, São Paulo, SP, Brazil.
Preparative Biochemistry & Biotechnology
|May 5, 2026
Summary
This study explored producing virus-like particles (VLPs) for SARS-CoV-2 vaccines. Co-infection with spike and nucleocapsid genes in insect cells successfully generated VLPs, crucial for vaccine development.
Area of Science:
- Biotechnology
- Virology
- Immunology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a global pandemic.
- Virus-like particles (VLPs) mimic native viruses and are potent immunogens, stimulating adaptive immunity.
- VLPs are promising candidates for vaccine development due to their safety and efficacy.
Purpose of the Study:
- To assess the expression of SARS-CoV-2 spike (S) and nucleocapsid (N) proteins.
- To evaluate Virus-Like Particle (VLP) production using a baculovirus-insect cell system.
- To compare VLP production in Schott flasks versus a stirred-tank bioreactor.
Main Methods:
- Utilized two monocistronic recombinant baculoviruses encoding SARS-CoV-2 S and N genes.
- Employed Sf9 insect cells in both Schott flasks and a stirred-tank bioreactor.
- Analyzed cell metabolism, virus titer, cell death, protein expression, and VLP formation.
Main Results:
- Significant differences in Sf9 cell metabolism, virus titer, and cell death were observed between culture systems.
- Expression of both S and N proteins was confirmed in both Schott flasks and bioreactors.
- Virus-like particle formation (69.1-78.2 nm) was exclusively confirmed in the co-infection setup.
Conclusions:
- Co-infection with baculoviruses encoding both SARS-CoV-2 S and N genes is essential for VLP production.
- The baculovirus-insect cell system is a viable platform for SARS-CoV-2 VLP generation.
- Further optimization of culture conditions may enhance VLP yield and quality for vaccine applications.
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