acute, highly contagious disease, 1510s, small pokkes, as distinguished from great pox "syphilis;" from small-pock "pustule caused by smallpox" (mid-15c.); see small (adj.) + pox. Compare French petite vérole. Fatal in a quarter to a third of unvaccinated cases, it could persist in clothes or other contaminated articles for months or years.
1800, used by British physician Edward Jenner (1749-1823) for the technique he publicized of preventing smallpox by injecting people with the similar but much milder cowpox virus (variolae vaccinae), from vaccine (adj.) "pertaining to cows, from cows" (1798), from Latin vaccinus "from cows," from vacca "cow," a word of uncertain origin. A mild case of cowpox rendered one immune thereafter to smallpox. "The use of the term for diseases other than smallpox is due to Pasteur" [OED].
The earlier 18c. method of smallpox protection in England was by a kind of inoculation called variolation (from variola, the medical Latin word for "smallpox"). There are two forms of smallpox: a minor one that killed 2% or less of the people who got it, and a virulent form that had about a 30% mortality rate and typically left survivors with severe scarring and often blinded them. Those who got the minor form were noted to be immune thereafter to the worse. Doctors would deliberately infect healthy young patients with a local dose of the minor smallpox, usually resulting in a mild case of it at worst, to render them immune to the more deadly form. Jenner's method was safer, as it involved no smallpox exposure.
"smallpox," 1771, medical Latin diminutive of Latin varius "changing, various," in this case "speckled, spotted" (see vary).
1803, "to inoculate with a vaccine," originally with cowpox for the purpose of procuring immunity from smallpox, back-formation from vaccination. Related: Vaccinated; vaccinating.
mid-15c., "implant a bud into a plant," from Latin inoculatus, past participle of inoculare "graft in, implant a bud or eye of one plant into another," from in- "in" (from PIE root *en "in") + oculus "bud," originally "eye" (from PIE root *okw- "to see"). Meaning "implant germs of a disease to produce immunity" is from inoculation, originally in reference to smallpox, after 1799, often used in sense of "to inoculate with a vaccine." Related: Inoculated; inoculating.