engleski

Towards an optimized measles virus replication using design of experiments

Measles vaccines are currently produced by standard cell culture techniques mainly in roller bottles or cell factories. A preresquisite for obtaining standardized and reproducible virus quality and quantity is an optimization of each step in the vaccine production process. With goal of increasing an overall process productivity we focused on optimization of the virus replication phase in measles virus vaccine production. An influence of five operating parameters on virus replication was assayed: cell age within a passage, necessity of trypsin removal during preparation of the cell suspension, cell seeding density, multiplicity of infection and media volume for virus harvests. Each factor was tested at two experimental levels. Experiments were set as a fractional factorial design consisting of 16 runs and were conducted on a lab-scale production system, 25 cm2 T- flask. A virus titer was determined in individual virus harvests collected from each T-flask. Based on obtained titer values, process capacity and productivity were derived as additional sensitive response variables. Main effects of selected factors on process responses were calculated by STATISTICA 6.1 software. The results show that multiplicity of infection has the major effect on the process capacity and productivity as response variables. These results present the basis for further optimization of measles virus replication.

replication, optimization, design of experiments

nije evidentirano