MODELING THE POPULATION-DYNAMICS OF BACULOVIRUS-INFECTED INSECT CELLS - OPTIMIZING INFECTION STRATEGIES FOR ENHANCED RECOMBINANT PROTEIN YIELDS

The insect cell-baculovirus model presented here is capable of simulating cell population dynamics, extracellular virion densities, and heterologous product titers in reasonable agreement with experimental data for a wide range of multiplicities of infection (MOI) and times of infection. The model accounts for the infection of a single cell by multiple virions and the consequences on the time course of infection. The probability of infection by more than one virion was approximated using the Poisson distribution, which proved to be a refinement over second-order kinetics. The model tracks initiation and duration of important events in the progression of infected cell development (virus replication, recombinant protein synthesis, and cell lysis) for subpopulations delineated by the time and extent of their initial infection. The model suggests infection strategies, weighing the importance of MOI and infection time. Maximum product titers result from infection in the early exponential growth phase with low MOI.