DESCRIPTION (provided by applicant): Influenza is a major cause of morbidity and mortality in nearly every year; when pandemics occur, the impact is even more severe. Influenza virus can now be engineered to create a virus of pandemic potential, and global spread of such a virus is probable. Vaccine is the first line of defense against influenza whatever its manifestation. Live-attenuated vaccine is now available, but its efficacy has not been evaluated in a trial with standard inactivated vaccine. Thus, it is not clear which of the two vaccines should be given priority, especially in terms of pandemic and emergency planning. We propose to study the efficacy of the two vaccines in a controlled trial using virologic endpoints. The intent is to evaluate not only the efficacy, but also the breadth and duration of immunity produced by the two vaccines. In the first two years of the three-year study, two participant groups will receive either live-attenuated or inactivated vaccine and a third group will receive a placebo preparation. Blood and specimens for virus identification will be collected. The primary outcome will be prevention of symptomatic laboratory-confirmed influenza meeting a case definition. In the third year, no vaccine or placebo will be given, but participants will continue to be followed to determine duration of protection. Additional laboratory studies will expand examination of the breadth of immunity, even if antigenic change does not occur in the course of the study. These studies will assist in determining whether it is useful to develop stockpiles of antigens or vaccines in anticipation of a future event. They will also examine potential markers of protection; these markers have been identified as being essential in evaluation of vaccines for use in pandemics. Results will help to determine how the vaccine may be used as part of the strategy to combat influenza in varying situations.