THE EFFICACY OF LIVE ATTENUATED, COLD-ADAPTED, TRIVALENT, INTRANASAL INFLUENZAVIRUS VACCINE IN CHILDREN

Background. Influenzavirus vaccine is used infrequently in healthy chi ldren, even though the rates of influenza in the group are high. We co nducted a multicenter, double-blind, placebo-controlled trial of a liv e attenuated, cold-adapted, trivalent influenzavirus vaccine in childr en 15 to 71 months old. Methods. Two hundred eighty-eight children wer e assigned to receive one dose of vaccine or placebo given by intranas al spray, and 1314 were assigned to receive two doses approximately 60 days apart. The strains included in the vaccine were antigenically eq uivalent to those in the inactivated influenzavirus vaccine in use at the time. The subjects were monitored with viral cultures for influenz a during the subsequent influenza season. A case of influenza was defi ned as an illness associated with the isolation of wild-type influenza virus from respiratory secretions. Results. The intranasal vaccine was accepted and well tolerated. Among children who were initially serone gative, antibody titers increased by a factor of four in 61 and 96 per cent, depending on the influenza strain. Culture-positive influenza wa s significantly less common in the vaccine group (14 cases among 1070 subjects) than the placebo group (95 cases among 532 subjects). The va ccine efficacy was 93 percent (95 percent confidence interval, 88 to 9 6 percent) against culture-confirmed influenza. Both the one-dose regi men (89 percent efficacy) and the two-dose regimen (94 percent efficac y) were efficacious, and the vaccine was efficacious against both stra ins of influenza circulating in 1996-1997, A(H3N2) and B. The vaccinat ed children had significantly fewer febrile illnesses, including 30 pe rcent fewer episodes of febrile otitis media (95 percent confidence in terval, 18 to 45 percent; P < 0.001). Conclusions. A live attenuated, cold-adapted influenzavirus vaccine was safe, immunogenic, and effecti ve against influenza A(H3N2) and B in healthy children. (C) 1998, Mass achusetts Medical Society.