Smallpox vaccine: A vaccine that contains a live virus called vaccinia that is used to prevent smallpox. The vaccine does not contain the variola virus that causes smallpox, but exposes the immune system to proteins that look like the virus so that an immune response occurs. Through the use of the vaccine, smallpox was eliminated from causing human infection in the world in 1977. Routine vaccination against smallpox ended in 1972. The level of immunity among persons who were vaccinated before 1972 is uncertain. In people exposed to smallpox who are not immune to the disease, the vaccine can lessen the severity of or even prevent the illness if given within 4 days of exposure.