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
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