The invention relates in various aspects to a synthetic chimeric vaccinia virus or compositions comprising such viruses, and the development and use of systems and methods for producing such synthetic chimeric vaccinia viruses. The synthetic chimeric vaccinia viruses are well suited, among others, as virus vaccines or to generate an oncolytic response and pharmaceutical formulations.本發明在各種態樣中係關於一種合成之嵌合牛痘病毒或包含此類病毒之組合物,及用於產生此類合成之嵌合牛痘病毒之系統及方法的研發及使用。該合成之嵌合牛痘病毒尤其非常適合作為病毒疫苗或產生溶瘤反應及醫藥調配物。