Many recombinant viral vectors for expression of ectopic antigens mimic a natural infection and can induce a robust immune response against certain pathogens and tumors. Host-restricted poxviruses and adenoviruses are among the more prominent vaccine strains considered for such approaches.
Modified vaccinia virus Ankara (MVA) belongs to the group of the poxviruses and was obtained by serial passaging of a vaccinia virus with a broad host range in chicken embryo fibroblasts. After passage 516, MVA was shown to have stably lost the capacity to replicate in human cells.
Preference for replication in nonmammalian cells confers a high degree of safety and allows application even in immunocompromised patients. However, as opposed to conventional live vaccine strains, there is no subclinical amplification at the site of injection. For this reason, host-restricted viruses are given in high numbers of infectious units per dose for full efficacy, and large production yields are essential for vaccine programs based on such vectors.
Currently, avian cells used for vaccine production processes are primary chicken embryo fibroblasts. However, to overcome limitations associated with material that has to be prepared freshly for each manufacturing lot, we have developed a continuous avian cell line, AGE1.CR.pIX, which originates from duck primary cells to avoid contamination with active endogenous retroviruses of chickens. AGE1.CR.pIX cells proliferate in true suspension in chemically defined media and are fully permissive for a spectrum of vaccine viruses. Scalable and transportable processes that yield high titers of MVA have been demonstrated in stirred tank and Wave bioreactors.