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

MVA is arguably the most promising virus vector due to its capacity to express a wide array of transgenes with correct post-translational modification and its immunogenicity in vivo along with its safety profile including host restriction in mammalian cells and attenuation in vivo. Both domestic and international legislations require that the ERA of virus-vectored vaccines be submitted and evaluated as part of MAA and clinical trial application. Of particular interest to the ERA is the characteristics of the MVA vector, its interaction with the host and the environment that may result in immediate or delayed risk to human and animal health as well as to the environment. The strong safety profile of MVA-vectored vaccines as well as its history of safe use as smallpox vaccine have stagnated research into aspects of the biology of the vector that are still poorly understood but also relevant for further optimization of the safety of MVA. Thus, there is an underlying assumption that MVA is so safe that studies aimed at risk characterization of the vector is either regarded as irrelevant or has been unequivocally addressed in scientific literature [42] .