Allan Watt Downie demonstrated in 1939 that the modern smallpox vaccine was serologically distinct from cowpox,[14] and vaccinia was subsequently recognized as a separate viral species.

[16] Ernest William Goodpasture, Alice Miles Woodruff, and G. John Buddingh grew vaccinia virus on the chorioallantoic membrane of chicken embryos in 1932.

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.

MVA-BN (also known as: Imvanex in the European Union; Imvamune in Canada; and Jynneos[40][41]) is a vaccine manufactured by Bavarian Nordic by growing MVA in cell culture.

[37] Vaccinia is infectious, which improves its effectiveness, but causes serious complications for people with impaired immune systems (for example chemotherapy and AIDS patients) or history of eczema, and is not considered safe for pregnant women.

In 1714 and 1716, two reports of the Ottoman Empire Turkish method of inoculation were made to the Royal Society in England, by Emmanuel Timoni, a doctor affiliated with the British Embassy in Constantinople,[79] and Giacomo Pylarini.

The procedure had been known in Boston since 1706, when preacher Cotton Mather learned it from Onesimus, a man he held as a slave, who – like many of his peers – had been inoculated in Africa before they were kidnapped.

[85] An account from letter by Lady Mary Wortley Montagu to Sarah Chiswell, dated 1 April 1717, from the Turkish Embassy describes this treatment: The small-pox so fatal and so general amongst us is here entirely harmless by the invention of ingrafting (which is the term they give it).

They make parties for this purpose, and when they are met (commonly fifteen or sixteen together) the old woman comes with a nutshell full of the matter of the best sort of small-pox and asks what veins you please to have opened.

I am patriot enough to take pains to bring this useful invention into fashion in England, and I should not fail to write to some of our doctors very particularly about it if I knew any one of them that I thought had virtue enough to destroy such a considerable branch of their revenue for the good of mankind, but that distemper is too beneficial to them not to expose to all their resentment the hardy wight that should undertake to put an end to it.

[86]In the early empirical days of vaccination, before Louis Pasteur's work on establishing the germ theory and Joseph Lister's on antisepsis and asepsis, there was considerable cross-infection.

From 1770 to 1772 Jenner received advanced training in London at St. George's Hospital and as the private pupil of John Hunter, then returned to set up practice in Berkeley.

But it is known for certain that in the years following 1770, at least six people in England and Germany (Sevel, Jensen, Jesty 1774, Rendall, Plett 1791) tested successfully the possibility of using the cowpox vaccine as an immunization for smallpox in humans.

[94] Additional vaccinations were performed and in 1798 Jenner published his work entitled An Inquiry into the Causes and Effects of the Variolae Vaccinae, a disease discovered in some of the western counties of England, particularly Gloucestershire and Known by the Name of Cow Pox.

Modern research suggests Jenner was trying to distinguish between effects caused by what would be recognised as a non-infectious vaccine, a different virus (e.g. paravaccinia/milker's nodes), or contaminating bacterial pathogens.

[98] A further source of confusion was Jenner's belief that fully effective vaccine obtained from cows originated in an equine disease, which he mistakenly referred to as grease.

[102][103] By 1800, Jenner's work had been published in all the major European languages and had reached Benjamin Waterhouse in the United States – an indication of rapid spread and deep interest.

After arrival, "other Spanish governors and doctors used enslaved girls to move the virus between islands, using lymph fluid harvested from them to inoculate their local populations".

The authors of the official World Health Organization (WHO) account Smallpox and its Eradication assessing Jenner's role wrote:[19]: 264 Publication of the Inquiry and the subsequent energetic promulgation by Jenner of the idea of vaccination with a virus other than variola virus constituted a watershed in the control of smallpox for which he, more than anyone else deserves the credit.As vaccination spread, some European countries made it compulsory.

[124] Louis T. Wright,[125] an African-American Harvard Medical School graduate (1915), introduced, while serving in the Army during World War I, intradermal, smallpox vaccination for the soldiers.

[citation needed] Sydney Arthur Monckton Copeman, an English Government bacteriologist interested in smallpox vaccine investigated the effects on the bacteria in it of various treatments, including glycerine.

[130] He later reported that glycerine killed the causative organisms of erysipelas and tuberculosis when they were added to the vaccine in "considerable quantity", and that his method was widely used on the continent.

5. c. 60) set an upper limit of 5,000 per gram, and rejected any batch of vaccine found to contain the causative organisms of erysipelas or wound infections.

[128] In the late 1940s and early 1950s, Leslie Collier, an English microbiologist working at the Lister Institute of Preventive Medicine, developed a method for producing a heat-stable freeze-dried vaccine in powdered form.

[138] Easy to use with minimum training, cheap to produce ($5 per 1000), using one quarter as much vaccine as other methods, and repeatedly re-usable after flame sterilization, it was used globally in the WHO Smallpox Eradication Campaign from 1968.

[143] On 21 April 2022, Public Services and Procurement Canada published a notice of tender seeking to stockpile 500,000 doses of smallpox vaccine in order to protect against a potential accidental or intentional release of the eradicated virus.

Jenner believed that both cowpox and smallpox were viruses that originated in the horse and passed to the cow,[149]: 52–53  and some doctors followed his reasoning by inoculating their patients directly with horsepox.

As medical researchers subjected viruses to serial passage, inadequate recordkeeping resulted in the creation of laboratory strains with unclear origins.

[155] Because the sample was collected at the end of the smallpox eradication campaign, scientists considered the possibility that horsepox is a strain of vaccinia that had escaped into the wild.

[157] Modern Brazilian vaccines with a documented introduction date of 1887, made from material collected in an 1866 outbreak of "cowpox" in France, are more similar to horsepox than other strains of vaccinia.