Vaccinia virus is closely related to the virus that causes cowpox; historically the two were often considered to be one and the same. The precise origin of vaccinia virus is unknown due to the lack of record-keeping, as the virus was repeatedly cultivated and passaged in research laboratories for many decades. The most common notion is that vaccinia virus, cowpox virus, and variola virus (the causative agent of smallpox) were all derived from a common ancestral virus. There is also speculation that vaccinia virus was originally isolated from horses, and analysis of DNA from an early (1902) sample of smallpox vaccine showed that it was 99.7% similar to horsepox virus.
Vaccinia virus infection is typically very mild and often does not cause symptoms in healthy individuals, although it may cause rash and fever. Immune responses generated from a vaccinia virus infection protects the person against a lethal smallpox infection. For this reason, vaccinia virus was, and still is, being used as a live-virus vaccine against smallpox.
Vaccinia is also used in recombinant vaccines, as a vector for expression of foreign genes within a host, in order to generate an immune response.