A Phase I, randomized controlled clinical trial to study the reactogenicity and immunogenicity of a new split...

Area of Science:

• Biotechnology
• Vaccinology
• Cell line development

Background:

• The development of robust cell lines is crucial for vaccine production.
• Influenza vaccines are traditionally produced in eggs, which can present limitations.
• Ensuring the safety and suitability of cell lines for vaccine manufacturing is paramount.

Purpose of the Study:

• To evaluate the non-tumorigenic potential of the MDCK-derived BV-5F1 cell line for vaccine production.
• To establish a large-scale influenza virus production process using the BV-5F1 cell line.
• To assess the immunogenicity and safety of an influenza vaccine derived from cell culture in a Phase I clinical study.

Main Methods:

• Non-tumorigenicity testing of BV-5F1 cells according to FDA guidelines.
• Large-scale influenza virus production involving cell expansion on microcarriers in stirred fermenters, followed by virus infection.
• Purification of viral particles using ultracentrifugation and ultrafiltration, followed by formaldehyde inactivation to produce a split inactivated vaccine.
• A randomized, double-blind, Phase I clinical study in healthy adults to evaluate the bivalent cell culture-derived influenza vaccine.

Main Results:

• The BV-5F1 cell line demonstrated non-tumorigenic properties.
• The cell line was confirmed to be free of microbial and viral contaminants.
• The developed process enabled large-scale production of influenza virus.
• The Phase I clinical study showed the cell culture-derived split influenza vaccine to be highly immunogenic and safe in adults.

Conclusions:

• The BV-5F1 cell line is a safe and suitable substrate for the production of influenza vaccines.
• Cell culture-derived influenza vaccines present a viable alternative to egg-based production.
• The demonstrated immunogenicity and safety profile support further clinical development of this cell culture-derived influenza vaccine.