Smallpox vaccine was successfully maintained in cattle starting in the 1840s, and calf lymph vaccine became the leading smallpox vaccine in the 1880s. First-generation vaccines grown on the skin of live animals were widely distributed in the 1950s–1970s to eradicate smallpox. Second-generation vaccines were grown in chorioallantoic membrane or cell cultures for greater purity, and they were used in some areas during the smallpox eradication campaign. Third-generation vaccines are based on attenuated strains of vaccinia and saw limited use prior to the eradication of smallpox.All three generations of vaccine are available in stockpiles. First and second-generation vaccines contain live unattenuated vaccinia virus and can cause serious side effects in a small percentage of recipients, including death in 1–10 people per million vaccinations. Third-generation vaccines are much safer due to the milder side effects of the attenuated vaccinia strains. Second and third-generation vaccines are still being produced, with manufacturing capacity being built up in the 2000s due to fears of bioterrorism and biological warfare. First-generation
The first-generation vaccines are manufactured by growing live vaccinia virus in the skin of live animals. Most first-generation vaccines are calf lymph vaccines that were grown on the skin of cows, but other animals were also used, including sheep. The development of freeze-dried vaccine in the 1950s made it possible to preserve vaccinia virus for long periods of time without refrigeration, leading to the availability of freeze-dried vaccines such as Dryvax. : 115 The vaccine is administered by multiple puncture of the skin (scarification) with a bifurcated needle that holds vaccine solution in the fork.
All English stocks held at St Marys Hospital, London were transferred to more secure facilities at Porton Down and then to the U.S. at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia in 1982, and all South African stocks were destroyed in 1983. By 1984, the only known stocks were kept at the CDC in the U.S. and the State Research Center of Virology and Biotechnology (VECTOR) in Koltsovo, Russia. : 1273–76  These states report that their repositories are for possible anti-bioweaponry research and insurance if some obscure reservoir of natural smallpox is discovered in the future. Anti-terrorism preparation
Among more than 270,000 US military service members vaccinated with smallpox vaccine between December 2002, and March 2003, eighteen cases of probable myopericarditis were reported (all in first-time vaccinees who received the NYCBOH strain of vaccinia virus), an incidence of 7.8 per 100,000 during the 30 days they were observed. All cases were in young, otherwise healthy adult white men and all survived.In 2002, the United States government started a program to vaccinate 500,000 volunteer health care professionals throughout the country. Recipients were healthcare workers who would be first-line responders in the event of a bioterrorist attack. Many healthcare workers refused or did not pursue vaccination, worried about vaccine side effects, compensation and liability. Most did not see an immediate need for the vaccine. Some healthcare systems refused to participate, worried about becoming a destination for smallpox patients in the event of an epidemic.