Polio and rabies vaccines produced in continuous cell lines: a reality for Vero cell line.

The Vero cell line was applied to the production of Enhanced-Inactivated Polio Vaccine (E-IPV), Oral Polio Vaccine (OPV) and Rabies Vaccine, also called Purified Vero Rabies Vaccine (PVRV) for humans. The cell line was expanded through the cell bank systems. Using a microcarrier culture technique, a large-scale production combined with an efficient purification process was developed. An extensive study of purity and biological safety was applied to the cell line to validate several Manufacturer's Working Cell Banks. Special emphasis was laid on the absence of any virus in the cells or any trace of viral sequence included in the Vero cell genome. Sensitive tests were applied to check that residual cellular DNA was as low as possible per dose of vaccine. E-IPV was licensed in July 1982 and since 1983 more than 20 million doses have been inoculated into children, without any side-effects. The production capacity of this E-IPV is presently more than 60 million doses per year. For PVRV, the license was delivered in June 1985 and over 350,000 doses have been injected without any problem. For the OPV, 27 monovalent lots were produced, 9 lots for each serotype. The studies of RNA sequences in variable regions and viral proteins gave results similar to the OPV produced from primary monkey kidney cells. All the other tests, and especially the neurovirulence tests in live monkeys showed that the OPV produced in Vero cell lines was acceptable. Since the completion of clinical studies, the license has been pending. The quality of the Vero cell line, as produced and tested by the "Institut Mérieux", combined with the safety afforded by the virus purification, has helped to prevent potential problems.