Why did cowpox vaccination protect James Phipps from smallpox?

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Infographic showing estimated lives saved by childhood vaccinations worldwide from 1974 to 2024, with syringe-shaped bars for each disease. Measles tops the list at 93.71 million lives saved, followed by tetanus, whooping cough, and others, for a total of 153.84 million lives saved. — vaccine Vaccines and the estimates of lives saved over the period 1974–2024.

James Phipps was protected from smallpox because the cowpox and smallpox viruses share common antigens (proteins).1

When Edward Jenner inoculated Phipps with material from a cowpox lesion, these shared proteins activated the boy’s immune system. This process, known as cross-immunity, allowed his body to recognize and defend against the related smallpox virus when he was later exposed to it. Because the cowpox virus is closely related to the virus that causes smallpox, the initial infection provided effective protection without the severe risks associated with contracting smallpox itself.12