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

We have found that our MDCK-derived cell line (BV-5F1) is non-tumorigenic in tests conducted in accordance with FDA guidelines, and thus may be suitable for producing live, attenuated or inactivated vaccine. The cell line has been extensively tested for the presence of contaminating microorganisms. No infectious agents of viral or other microbial origin were present. Using the BV-5F1 cell line, we have now designed a process for the large-scale production of influenza virus for the manufacture of a vaccine. The production system involves expansion of cells anchored on a microcarrier using stirred fermenters, followed by virus infection. Viral particles are purified in a way similar to the licensed egg-derived vaccine Fluviral SF and mainly involves ultracentrifugation, ultrafiltration and formaldehyde inactivation. The final product is a split inactivated vaccine. A randomized, double-blind clinical study was made in healthy adults using the new split influenza vaccine derived from viruses grown in cell culture (bivalent formulation). The results of this Phase I study have demonstrated that the split influenza vaccine derived from cell culture is highly immunogenic and safe in adults.