The Ankara strain was taken to West Germany in 1953, where Herrlich and Mayr grew it on chorioallantoic membrane at the University of Munich. After 572 serial passages, the vaccinia virus had lost over 14% of its genome and could no longer replicate in human cells. MVA was used in West Germany in 1977–1980, but the eradication of smallpox ended the vaccination campaign after only 120,000 doses.MVA stimulates the production of fewer antibodies than replicating vaccines. During the smallpox eradication campaign, MVA was considered to be a pre-vaccine that would be administered before a replicating vaccine to reduce the side effects, or an alternative vaccine that could be safely given to people at high risk from a replicating vaccine. : 585  Japan evaluated MVA and rejected it due to its low immunogenicity, deciding to develop its own attenuated vaccine instead. In the 2000s, MVA was tested in animal models at much higher dosages. When MVA is given to monkeys at 40 times the dosage of Dryvax, it stimulates a more rapid immune response while still causing lesser side effects. MVA-BN (also known as: Imvanex in the European Union; Imvamune in Canada; and Jynneos) is a vaccine manufactured by Bavarian Nordic by growing MVA in cell culture. Unlike replicating vaccines, MVA-BN is administered by injection via the subcutaneous route and does not result in a vaccine "take." It is safer for immunocompromised patients and those who are at risk from a vaccinia infection. MVA-BN has been approved in the European Union, Canada, and the United States.
The second-generation vaccines are also administered through scarification with a bifurcated needle, and they carry the same side effects as the first-generation vaccinia strain that was cloned. However, the use of eggs or cell culture allows for vaccine production in a sterile environment, while first-generation vaccine contains skin bacteria from the animal that the vaccine was grown on.Ernest William Goodpasture, Alice Miles Woodruff, and G. John Buddingh grew vaccinia virus on the chorioallantoic membrane of chicken embryos in 1932. The Texas Department of Health began producing egg-based vaccine in 1939 and started using it in vaccination campaigns in 1948.: 588  Lederle Laboratories began selling its Avianized smallpox vaccine in the United States in 1959. Egg-based vaccine was also used widely in Brazil, New Zealand, and Sweden, and on a smaller scale in many other countries. Concerns about temperature stability and avian sarcoma leukosis virus prevented it from being used more widely during the eradication campaign, although no increase in leukemia was seen in Brazil and Sweden despite the presence of ASLV in the chickens. : 588 Vaccinia was first grown in cell culture in 1931 by Thomas Milton Rivers. The WHO funded work in the 1960s at the Dutch National Institute for Public Health and the Environment (RVIM) on growing the Lister/Elstree strain in rabbit kidney cells and tested it in 45,443 Indonesian children in 1973, with comparable results to the same strain of calf lymph vaccine.