| 摘要 |
2095428 9207958 PCTABS00013 The present invention concerns a method of evaluating the safety of live attenuated vaccines which is based on detection and measurement of the incidence of genetic changes associated with reversion to virulence in vaccine microorganisms. The method based on PCR and restriction enzyme analysis was developed and used for determination of the proportion of mutants contributing to neurovirulence of type 3 live oral poliovirus vaccine. The correlation between the neurovirulence of OPV lots revealed by the monkey test and the abundance of mutant virus containing cytidine in the positon 472 was discovered. The amount of these mutants increases upon passages of the virus in cell cultures at a rate dependent on the cell type, cultivation conditions and the seed virus stock. The present invention can be applied for the safety test of lots of live vaccines and in-process control of vaccine manufacturing as well as the approach for the optimization of conditions for manufacturing of safe vaccine and selection of the seed virus and cell substrate. |
