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How do shared antigens between vaccinia and variola create immunity to smallpox?

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Smallpox vaccination — smallpox Edward Jenner vaccinating his child against smallpox; colored engraving.

The immunity to smallpox provided by the vaccinia virus is a classic example of cross-immunity, a phenomenon where exposure to one virus confers protection against a related viral disease.1

Vaccinia and variola (the virus that causes smallpox) are both orthopoxviruses and share many surface antigens. When a person is vaccinated, the vaccinia virus stimulates the adaptive immune system to produce antibodies and memory B and T lymphocytes that are specifically programmed to recognize these shared surface structures.1

Because the immune system has been "trained" to identify these common antigens, it can effectively recognize and neutralize the variola virus if the vaccinated individual is later exposed to it. This robust immune response prevents the development of smallpox without the individual having to suffer the risks associated with the actual disease.21