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

The virus/vector/transgene can potentially be dispersed throughout the body when administered via a route other than the alimentary canal and this has potential of transmission to sex cells (with the attendant risk of transmission to offspring). MVA can reach target tissues other than the site of administration [153, 154] . However, being multiplication incompetent, MVA is rapidly cleared from the tissues [155, 156] . In situations where genetic modification has altered tissue tropism of the GMV, biodistribution will be affected especially for multiplication competent GMVs and this can result in infection of cells that are naturally not permissive to the original parental virus. This information is relevant for mapping the dissemination of the recombinant vector. Biodistribution may also influence the time window and routes of shedding of the virus from the recipient and thus, the likelihood of transmission to third parties including vertical transmission and transmission of the vector/recombinant vaccine to other individuals and host species. Further, it is important to map the biodistribution of the virus/vector/recombinant vaccine in immune-compromised individuals given that biodistribution in the immune-compromised is expected to differ from that of the immune-competent individuals. This will provide valuable data on how such recombinant vaccines may affect those with impaired immune system.