Hazard Characterization of Modified Vaccinia Virus Ankara Vector: What Are the Knowledge Gaps?

Okeke, Malachy I.; Okoli, Arinze S.; Diaz, Diana; Offor, Collins; Oludotun, Taiwo G.; Tryland, Morten; Bøhn, Thomas; Moens, Ugo

Different variants of VACV were used for vaccination against smallpox. MVA was originally generated by serial passages of chorioallantois Vaccinia virus Ankara (CVA) in chicken embryo fibroblast cells (CEF). It was produced in the Bavarian State Vaccine Institute (Germany) during 1968-1985 and used as a human smallpox vaccine [43] . The serial passages (>570 times) of the virus in CEF cultures resulted in major deletions and mutations in the viral genome, with a loss of approximately 30 kbp [44] . These modifications also affected virulence and immune evasion functions [45] [46] [47] , resulting in a highly attenuated vaccine virus that produced a low degree of adverse effects on the vaccinees [48] . A complete replication cycle of MVA is restricted to avian cells. In human and other mammalian cells, the virus replicates its DNA, has unimpaired expression of early and intermediate genes as well as most late genes but has a block at the stage of virion assembly [34] and thus cannot produce infectious progeny [49] [50] [51] [52] . However, MVA is still able to express viral genes, including inserted genes (i.e., encoding antigens to which the vaccine is directed) and thus stimulate the immune system of the recipient in a relevant way.