A recent study published in Genome Biology has explored the early history of smallpox vaccination by sequencing DNA from smallpox vaccination kits dating back to the American Civil War, from the Mütter Museum of the College of Physicians of Philadelphia.

The beginnings of vaccination are usually credited to Edward Jenner in England in 1796, although various people had previously observed that milkmaids who had been infected with cowpox were immune to infection from smallpox. Jenner took pus from cowpox lesions from the milkmaid Sarah Nelmes and inoculated it into an 8-year-old boy, James Phipps. He subsequently injected Phipps with material from a smallpox infection, and Phipps did not go on to develop smallpox. The process quickly caught on in the United Kingdom, and rapidly spread to the rest of Europe, and the United States. Because of the use of cowpox virus, the technique was called vaccination, from the Latin for cow, vacca.

In the 1930s, it was shown that the vaccinia virus used for vaccination was distinct from cowpox vaccine, and much later, genetic analyses showed that vaccinia was much closer to horsepox. The origins of vaccinia are therefore not clear. It is known that Jenner also experimented with horsepox virus for vaccination, but it is not known if early vaccination programs were performed with cowpox or horsepox. It is not known when vaccinia became the dominant virus used for vaccination; or whether it derived from horsepox or cowpox (or when this divergence might have occurred), or whether it was a third, independent virus.

Duggan and colleagues’ work attempts to shed light on this. They were given access to five vaccination kits dating to the middle of the 19th Century (most likely between 1859 and 1873). Four of the kits contained folding lancets, glass slides for mixing lymph, and tin boxes for storing scabs; the fifth was ‘The Automatic Vaccinator’, a tool designed for use with lymph or scabs smeared into a mixture on glass plates.

The team extracted material from the kits and sequenced the DNA. The viral sequences from the different kits cluster tightly together, suggesting that a narrow range of vaccine strains was in use in Philadelphia at this time. They also cluster with a vaccinia sequence from a commercial strain produced in Philadelphia in 1902, as well as with the one known genome of horsepox, in a clade among other vaccinia strains, and separate from cowpox sequences.

As well as the origin of vaccinia, this study sheds light on vaccination practices in the USA at the time. Early on, vaccine strains were spread by inoculating from person to person. The high number of human sequences extracted from the kits shows that that was the case here. Two of the five vaccine hosts were women. The authors were able to generate complete mitochondrial genomes from three of the kits, and these sequences were typical of western Eurasia. This is notable, because African American slaves were often used to propagate the virus, particularly in the southern states.

Although this study has not, ultimately, cleared up the origin of vaccinia, it has shown that not much more than 50 years after Jenner’s initial experiments, vaccinia, and not cowpox, was being used for vaccinations.

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