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Edward Jenner, the English physician who first developed the smallpox vaccine in 1796, believed that vaccination caused a fundamental change in a person's constitution and would lead to lifelong immunity to smallpox. Unfortunately, it is now clear that this immunity wanes over time. A vaccination received 40 years ago most likely does not protect you against smallpox infection today, although it may help prevent a fatal outcome.

It is difficult to determine exactly how long the smallpox vaccine provides defense against the virus. Limited research continues with virus samples at the Centers for Disease Control and Prevention in the U.S. and at a Russian government laboratory in Koltsovo, but smallpox infections no longer occur naturally. Thus, modern scientific techniques cannot be brought fully to bear on this question.