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

Since MVA is subjected to selection pressure (multiple multiplication cycles) during production of a high titer virus stock intended for vaccination, it is essential to examine the genome stability of the virus across MSV + 1 to MSV + 5 in human cell lines and in immune-competent and immune-compromised animal models. At present, this information is not provided in ERA dossiers submitted for clinical trials or MAA because relevant EU directive (Directive 2001/18/EC) has not made the provision of such data obligatory. Data on evolution of MVA in permissive cells during Good Manufacturing Practice (GMP) manufacturing will enable risk assessors to evaluate the genome stability of MVA and the presence of variants in the production batch intended for vaccination. The emergence of quasi-species and their role in the modulation of the MVA phenotype including host range, infectivity, attenuation, virulence and biodistribution is an omitted research field that needs to be addressed.