The influence of serial passage on the stability of an exogenous gene expression in recombinant baculovirus

The baculovirus expression system has been widely used for industrial‐scale production of recombinant proteins. These recombinant proteins are expressed from recombinant baculoviruses carrying an expression cassette for a particular protein. Even though the baculovirus genome can accommodate large fragments of foreign genetic material, it has been shown that defective interfering particles (DIs) are generated over many passages of the recombinant virus. Defective interfering particles can affect the stability of the inserted gene, which can result in sub‐optimal expression of the recombinant protein; this can, therefore, have a significant impact on production. The stability of exogenous genes in recombinant viruses over serial passage has not yet been investigated. As such, the present study set out to assess the effect of serial passage on the stability of the expression of an exogenous gene inserted into a recombinant baculovirus and its subsequent recombinant protein yield. To achieve this, a recombinant baculovirus carrying the classical swine fever virus E2 gene was serially passaged up to 20 times. The results showed that the E2 gene expression by the recombinant baculovirus was stable for up to 10 passages without any effect on recombinant E2 production in insect cells.