Smallpox Immunization in the 21st Century

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Abstract
Just over 6 months ago a decision was made to reinstitute smallpox vaccination for selected segments of the US population.1 This decision to implement a pre-event smallpox vaccination program was based on the concern that smallpox could be used as an agent of bioterrorism; however, certain questions about the risk of smallpox vaccination in a 21st-century setting arose.2,3 Among these was the possibility that the current United States population might be more vulnerable to serious adverse effects of the smallpox vaccine due to a relative increase—compared with 3 to 4 decades ago—in conditions affecting the immune system such as the use of immunosuppressive drugs and the presence of human immunodeficiency virus infection in the community. A consequence of this change in population profile could be an increased incidence of established adverse events as well as the emergence of heretofore unrecognized adverse events. At the same time that these issues were being raised, there was also an appreciation that the immunization of a new generation of individuals provided an opportunity to apply 21st-century technology to the study of vaccinia-induced immunity.