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

Studies on viral and host factors that modulate transgene stability are miniscule. With few exceptions, the effect of transgene insertion site [105] [106] [107] [108] , promoter choice [104] , promoter spacer length [109] , expression levels of the transgene [110] , timing of transgene expression [104] , sequence/structure of the transgene/flanking region [111] and host cell used for virus amplification [96] on transgene stability are poorly understood. Elucidating the virus and host determinants of transgene instability is essential as such knowledge will be deployed in designing transgenic MVA vaccines where the probability of transgene instability is extremely low or negligible. The few studies on transgene stability were done in established cell lines. To our knowledge, there is no report where transgene instability and the underlying mechanisms have been investigated in vivo. This is particularly relevant in immuno-compromised infection models. Immuno-compromised humans, domesticated animals and wildlife are population subsets that may be exposed to recombinant MVA vaccines, thus the stability of the transgene in immuno-compromised animal models should be investigated and data obtained should guide the ERA of recombinant MVA.