Quantification of cell culture factors affecting recombinant protein yields in baculovirus‐infected insect cells

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Abstract
An experimental study was undertaken to quantify the effects of infection cell density, medium condition, and surface aeration on recombinant protein yields in insect cells. In the absence of surface aeration and fresh medium, insect cells generated higher product yields (on a per cell basis) when infected with recombinant baculovirus at low cell densities, LCD (3 × 105−4 × 105 cells/mL), than at high cell densities, HCD (>0.9 × 106 cells/mL), for two distinct baculovirus types. Surface aeration of a HCD culture infected in spent medium improved β-glactosidase yields 5-fold over the nonaerated case. Surface aeration and medium replenishment improved β-galactosidase yields of a HCD culture by 20-fold (compared to a 1.6-fold improvement for a LCD culture), resulting in cultures with productivties that were independent of the cell density at infection.