Although smallpox no longer exists in the wild, vaccinia virus is still studied widely by scientists as a tool for gene therapy and genetic engineering.

In 1796, the British doctor Edward Jenner proved that an infection with the relatively mild cowpox virus would also confer immunity to the deadly smallpox.

Allan Watt Downie demonstrated in 1939 that the modern smallpox vaccine was serologically distinct from cowpox,[6] and vaccinia was subsequently recognized as a separate viral species.

[12] Therefore, the large genome is required for encoding various enzymes and proteins involved in viral DNA replication and gene transcription.

On the other hand, the CEV is believed to play a role in cell-to-cell spread and the EEV is thought to be important for long range dissemination within the host organism.

Kim and Sharp demonstrated MR of vaccinia virus after treatment with UV-light,[15] nitrogen mustard,[16] and X-rays or gamma rays.

[additional citation(s) needed] Vaccinia contains within its genome genes for several proteins that give the virus resistance to interferons:

Manufactured by Sanofi Pasteur, the U.S. Centers for Disease Control and Prevention stockpiled 192.5 million doses of the new vaccine (see list of common strains below).

[26] A smallpox vaccine, Imvanex, which is based on the Modified vaccinia Ankara strain, was approved by the European Medicines Agency (EMA) in 2013.

[citation needed] 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.

In 1913, E. Steinhardt, C. Israeli, and R. A. Lambert grew vaccinia virus in fragments of pig corneal tissue culture.

[32]A paper published in 1915 by Fredrick W. Twort, a student of Willian Bulloch, is considered to be the beginning of modern phage research.

[36] The boy developed the telltale rash over 80 percent of his body after coming into close contact with his father, who was vaccinated for smallpox before being deployed overseas by the United States Army.

[36] In 2010, the Centers for Disease Control and Prevention (CDC) reported that a woman in Washington had contracted vaccinia virus infection after digital vaginal contact with her boyfriend, a military member who had recently been vaccinated for smallpox.

The CDC indicated that it was aware of four similar cases in the preceding 12 months of vaccinia infection after sexual contact with a recent military vaccinee.