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

Worst-case assumptions that can be tested and eventually rejected or proven are an essential sub-step in the risk characterization of GMOs including genetically modified viruses [199] and plants [200] . The steps used for the ERA of GMVs outlined in Section 1.2 do not have a probabilistic distribution for the frequency of an adverse effect and the level of consequences associated with the adverse effect. Rather, the rating of risk as negligible, low, moderate or high is largely based on weight of evidence (WOE) from peer-reviewed literature and "expert" opinion from scientists commissioned by regulatory agencies like EMA. Much of the published literature on MVA-vectored vaccine addresses vaccine efficacy rather than aspects relevant to ERA. Testing for worst-case scenarios that are falsifiable will reduce uncertainty since a risk analysis where the worst-case scenario is shown not to occur is evidence that the risk of adverse effect is low. In the case of MVA-vectored vaccines, assumptions of worst-case scenarios such as recombination with wild-type OPVs and emergence of more virulent hybrid progenies should be falsified or rejected through experimental investigation in authentic immuno-compromised and immuno-competent animal models.