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 Th1 cytokine profile is characterized by IFNγ, Interleukin (IL)-2 and IL-12 production, while IL-4, IL-5, IL-6, IL-10 and IL-13 are typical for a Th2 response [178, 179] . Infection/immunization with MVA or recombinant MVA can provoke Th1 responses and deletion of MVA genes can further increase these responses. For example, levels of the Th1 cytokines IFN-γ, IL1B, IL-12 were significantly higher in mice inoculated with MVA∆C12L/A44L-A46R than in animals challenged with MVA [180] . A higher frequency of IFN-γ, TNF-α and IL-2 secreting E3-specific CD8+ T-cells was observed 8 weeks after vaccination with MVA lacking B15R compared to MVA [181] . MVA-C, a MVA vector that expressed the envelope protein and the Gag-Pol-Nef from HIV-1 subtype C induced IFN-γ producing CD8+ T cells. The number of these T cells was higher upon infection with a mutant lacking the F1L gene [182] . When genes encoding for co-stimulatory molecules and cytokines are inserted into the MVA vector in order to improve immunogenicity, evidence has to be provided to show that the molecules do not predominantly result in a Th2 response. In multiplication competent OPV vectors, insertion of IL-4 resulted in increased pathogenicity of the recombinant virus [183] due to the inhibition of Th1 response [184] . At present, provision of cytokine profile data is not obligatory for the ERA of MVA and MVA-vectored vaccines. However, provision of such a data is important for evaluating the risk of potential reversion of the MVA vector to wild type.