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

In transmission to non-target hosts, persons considered at risk of exposure to virus vector/virus-vectored vaccine are those that come in close contact with the vaccinee. These often are family members, health care workers as well as pets and other animals in close contact with the vaccinee. Knowledge about biodistribution, shedding and the immunological status of the vaccinee close contacts will help in identifying the route of transmission. If the virus-vector is inadvertently transmitted to these individuals, clearance should be effective given that a good proportion of the population already have pre-existing immunity to VACV/MVA. However, should the close contacts have compromised immunity due to old age, very young, sick or are on immunosuppressive drugs, clearance may be inefficient and the consequences of infection might be more significant. In these individuals, interactions (exchange of genetic materials, helper functions of gene products/factors) between GM virus vector and resident natural viruses could generate quasi virus species that are unstable and constantly mutate. This could lead to species with altered epitopes and thus less infectivity [164] . Altered epitope can result in less efficient immune clearance due to weak binding to receptors on the immune cells and can lead to establishment of chronic, latent or persistent infections. A situation in which non-neutralizing antibodies facilitate the infection of other cells (antibody-dependent enhancement of infection) may arise [165, 166] . With respect to MVA/MVA-vectored vaccines, the potential for transmission to non-target hosts is low due to its multiplication incompetence in most mammalian cells. However, this observation should be demonstrated in vitro in relevant cell cultures, as well as in both immune-competent and immune-deficient animals for each MVA-vectored vaccine. This will confirm that multiplication competence has not been restored in the recombinant MVA vaccine.