Efficacy of live attenuated influenza vaccine in children: A meta-analysis of nine randomized clinical trials.

Nine randomized clinical trials, including approximately 25,000 children aged 6-71 months and 2000 children aged 6-17 years, have evaluated the efficacy of live attenuated influenza vaccine (LAIV) against culture-confirmed influenza as compared to placebo or trivalent inactivated vaccine (TIV). We conducted meta-analyses, based on Mantel-Haenszel relative risks from fixed effect models, to provide an estimate of vaccine efficacy (VE). Relative to placebo, year 1 VE for two doses in vaccine-naïve young children was 77% (95% CI: 72%, 80%; P<0.001) against antigenically similar strains and 72% against strains regardless of antigenic similarity. Efficacy was 85%, 76%, and 73% against antigenically similar A/H1N1, A/H3N2, and B, respectively. Year 1 VE of one dose against antigenically similar strains in vaccine-naive children was 60%; efficacy of one dose in previously vaccinated children in year 2 of the various studies was 87%. In head-to-head trials comparing two doses of TIV and LAIV, vaccine-naïve children who received two doses of LAIV experienced 46% fewer cases of influenza illness caused by antigenically similar strains. Similarly, for studies including older children who had been previously vaccinated, those receiving one LAIV dose experienced 35% fewer cases of influenza illness than those receiving one TIV dose. LAIV showed high VE versus placebo with no evidence of difference by age or by circulating subtype. In these studies, LAIV was more effective than TIV.