Variolation shortly after variolation began to outweigh the benefits of the procedure. From the 1760s, a number of individuals, including John Fewster, Peter Plett, Benjamin Jesty, and particularly Edward Jenner, were interested in the use of material from cowpox, an animal infection, to protect against smallpox. In 1796, Jenner vaccinated James Phipps, did more vaccinations in 1798, and was the first to publish evidence that cowpox protected against smallpox, was safer than variolation, and that his vaccine could be maintained by arm-to-arm transfer. The use of variolation soon began to decline as the smallpox vaccine became widely used and its benefits
Smallpox vaccine lost its potency at ambient temperatures which restricted its use in tropical climates. However, it remained in use into the 1970s where a satisfactory cold chain was available. Animals continued to be widely used by vaccine producers during the smallpox eradication campaign. A WHO survey of 59 producers, some of whom used more than one source of vaccine, found that 39 used calves, 12 used sheep and 6 used water buffalo, whilst only 3 made vaccine in cell culture and 3 in embryonated hens' eggs. English vaccine was occasionally made in sheep during World War I but from 1946 only