The poxviral replication cycle occurs entirely in the cytoplasm and as such exposes its genomic DNA to cytosolic DNA sensors. Perhaps the most important among these is cyclic 2’-3’-GMP-AMP synthase (cGAS) which generates its secondary messenger cyclic 2’-3’-GMP-AMP (cGAMP) upon binding aberrant cytosolic DNA. This molecule is crucial for inducing antiviral signalling in directly infected and bystander cells. As such orthopoxviruses (OPXV) have obtained cGAMP nucleases to inactivate this signalling by linearising cGAMP. Poxviruses have been used as vaccines for centuries and recent efficient human-to-human transmission of monkeypox virus underlines the ongoing need for efficacious poxviral vaccines. This thesis sought to improve the attenuated poxviral vaccine vector, modified vaccinia Ankara (MVA) by arming it with cGAS to enhance cGAMP production and immunogenicity. To avoid selective pressure against this key signalling molecule, self-adjuvanting MVA (saMVA) was generated in a BHK21 cell line rendered deficient for DNA sensing by genome editing. The ability of saMVA and its control viruses to induce innate immune signalling was assessed in vitro and in vivo. saMVA was able to induce higher activation of antiviral signalling and induced higher production of immune signalling molecules than control viruses in target cells. Transcriptomic analysis of infected primary human macrophages indicated higher production of important cytokines compared to conventional MVA. Finally, saMVA induced a more robust T cell response than conventional MVA in a mouse model. The cGAMP nuclease in many OPXV is fused to a schlafen domain, likely acquired by horizontal gene transfer from a host cell but the role of this fusion has not been established. This thesis aimed to attribute a function to the schlafen domain. Despite not directly contributing to the inhibition of DNA sensing in reporter assays it was demonstrated that the schlafen domain did interact with DNA which may mediate effective function of this immunomodulator.