Smallpox is an acute contagious disease caused by variola virus, a member of the Orthopoxvirus family. Smallpox, which is believed to have originated over 3,000 years ago in India or Egypt, was one of the most devastating diseases known to humanity. Smallpox is transmitted from person to person by infected aerosols and air droplets spread in face-to-face contact with an infected person. The disease can also be transmitted by contaminated clothes and bedding, though the risk of infection from this source is much lower.

Following an incubation period of about 12-14 days there is a sudden onset of influenza-like symptoms including fever, malaise, headache, prostration, severe back pain and, less often, abdominal pain and vomiting. Two to three days later, a characteristic rash appears, first on the face, hands and forearms and then after a few days progressing to the trunk. Lesions also develop in the mucous membranes of the nose and mouth, and ulcerate very soon after their formation, releasing large amounts of virus into the mouth and throat. Two forms of the disease are recognized, variola minor with a mortality rate of approximately 1%, and the more common variola major with a mortality rate of 30%. Between 65–80% of survivors are marked with deep pitted scars (pockmarks), most prominent on the face.

In 1967, WHO launched an intensified plan to eradicate smallpox. Following a successful campaign to achieve high levels of immunization globally, the last case of endemically circulating smallpox occurred in 1977. In 1979, WHO recommended that vaccination against smallpox be stopped in all countries, the only exception being special groups, such as researchers working with smallpox and related viruses.

The global eradication of smallpox was certified in December 1979 and endorsed by the World Health Assembly in 1980, marking one of the most successful collaborative public health initiatives in history. Following eradication, smallpox, vaccine production was halted. A large stock of the smallpox vaccine was retained around the world although the storage conditions and potency of these stocks are not known. Two sites in the USA and Russia hold stocks of variola virus. In the interest of global security, these stocks were to be destroyed by the end of the twentieth century. However, due to continued interest in research and development involving variola virus, the destruction of the remaining stocks of smallpox virus has been postponed by the World Health Assembly.

Smallpox Vaccines

Edward Jenner demonstrated, in 1798, that inoculation of humans with live vaccinia virus (cowpox) could protect against smallpox. This brought the first hope that the disease could be controlled. Vaccinia vaccine has been used continuously since then. Most existing vaccine stocks and the vaccine utilized by the WHO eradication campaign consisted of pulp scraped from vaccinia-infected animal skin, mainly calf or sheep, with phenol added to a concentration sufficient to kill bacteria, but not so high as to inactivate the vaccinia virus. The live vaccine was then freeze-dried and sealed in ampoules for later re-suspension in sterile buffer and subsequent intradermal inoculation by multiple puncture with a bifurcated needle. The vaccinia virus is remarkably stable when lyophilized, and vaccines stored under appropriate conditions for as long as 18 years have not lost their potency.

A number of new vaccines produced on cell substrates rather than animal skin have been developed following renewed interest in the production and use of smallpox vaccines.

Smallpox vaccine standardization

Written Standards

WHO recommendations for the production and quality control of smallpox vaccines were first adopted in 1959 and revised in 1965. They were updated in 2003 in case new supplies of vaccine were required. This update includes production on cell substrates and introduces modern requirements for adventitious agent testing.

Reference materials

A WHO reference material for smallpox vaccine (vaccinia) is available to qualified applicants:

Meeting reports

Related information

Last update:

13 January 2014 16:00 CET