Efficacy against mild influenza for A/H3N2 and B strains was 94.3% (76.1, 99.4) and 83.9% (35.5, 97.2), respectively. Study 2 enrolled a total of 4166 children ≥24 months of age (LAIV, n = 2083; placebo, n = 2083). The attack rate of moderate/severe influenza was 2.1% (43/2083) in the LAIV HA-1077 solubility dmso group versus 4.3% (90/2083) in the IIV group, resulting in a relative efficacy

of LAIV compared with IIV of 52.2% (31.6, 66.6). The attack rate of mild influenza, after exclusion of moderate or severe cases, was 4.1% (84/2040) in the LAIV group versus 7.5% (149/1993) in the placebo group, resulting in a relative efficacy of 45.0% (28.6, 57.5) ( Fig. 1C). Efficacy against moderate/severe influenza for A/H1N1, A/H3N2, and B was 100% (−9.1, 100), 80.9 (60.5, 91.7), and 10.3 (−45.4, 44.8), respectively. Efficacy against mild influenza for A/H1N1, A/H3N2, and B was 91.7% (66.4, 99.0),

59.1% (35.1, 74.9), and 13.6% (−25.0, 40.5). Children are considered a priority group for vaccination because of the high burden of influenza disease among children and the availability Alpelisib cell line of safe and effective vaccines. Vaccinating children against influenza also can indirectly protect other age groups against influenza. Public health agencies promote vaccination against influenza in children because they have been identified as the main spreaders of influenza infection [7]. From this perspective, it is important to prevent any influenza

case, independent of disease severity. To best characterize a vaccine’s effect on influenza transmission, influenza vaccine efficacy should be assessed against all shedding influenza infections, whether severe or mild, symptomatic or not [13]. Although several clinical very trials have documented the efficacy of LAIV in children [9], this study is the first evaluation of LAIV efficacy as a function of disease severity. LAIV was efficacious against moderate/severe influenza and against milder influenza. LAIV was also significantly more efficacious than IIV for influenza A disease of all severity levels. The lack of LAIV superiority relative to IIV for influenza B in the current analysis may be due to the fact that a significant proportion of influenza B cases were due to antigenic variant strains. Two other IIV-controlled studies of LAIV in children demonstrated LAIV superiority against matched B strains [14] and [15]; however, neither of these studies collected data on disease severity. Together with the recent study demonstrating high levels of IIV efficacy only against moderate/severe influenza A disease, the results of this analysis show that LAIV provides children with a high degree of protection against influenza A and B illness of all severity levels and thus should be effective in interrupting influenza transmission by children in the community.