However, when the antigenic difference between the vaccine and circulating A/H3N2 strains is considerable, as occurred with emergence of the A/Fujian variant in 2003, LAIV efficacy may be reduced

[10] and [25]. LAIV efficacy after revaccination in year 2 with a single dose was consistently higher compared with the efficacy of 2 doses in year 1, which is likely due to continuing immunity from the first season vaccination [26]. The sustained duration of LAIV protection in children has been described previously. In 1 study in Dabrafenib concentration Asia in which influenza circulated through 13 months after vaccination, LAIV efficacy was 74% (95% CI: 40, 89) during late-season outbreaks that occurred 5.5–13 months after vaccination, which

was similar to the 69% (95% CI: 53, 80) efficacy observed for the season overall [27]. Analyses of LAIV efficacy by various subject characteristics demonstrated LAIV is highly efficacious in male and female children as well as across multiple geographic regions. The finding of higher efficacy in female subjects in year 1 of placebo-controlled studies is not readily explained; the lack of a difference in year 2 of placebo-controlled studies Panobinostat suggests that the difference could be due to chance alone and not a true biologic difference. Even if true, the difference would have no clinical relevance given that LAIV provided greater efficacy compared with TIV in both male and female subjects. The impact of subject age on LAIV efficacy was not evaluated in the current either analysis. Additionally, data for children and adolescents 7 through 17 years of age is limited to one single-season study that compared LAIV and TIV. However, a previous analysis of LAIV efficacy by age in studies with broad enrollment age ranges demonstrated that LAIV efficacy does not decline with increasing age or repeated exposure to influenza in children up to 17 years

of age [28]. In addition to the incidence of culture-confirmed influenza illness, all of the studies in the current analysis that were conducted in children 6 years of age and younger prospectively evaluated the incidence of acute otitis media (AOM). Among children 24–71 months of age, LAIV reduced the incidence of influenza-associated AOM by 91% (95% CI: 84, 96) relative to placebo and 62% (95% CI: 21, 83) relative to TIV. Additionally, LAIV reduced the severity of influenza illness among breakthrough cases in children 24–71 months of age, as the rate of AOM among subjects with influenza was 57% (95% CI: 19, 79) lower among LAIV recipients relative to placebo recipients [29]. As expected, significant heterogeneity was demonstrated in some comparisons. This can be explained by slight variations in the trials with regard to circulating strains during different influenza seasons, previous exposure of participants to influenza vaccination or disease, and other factors.