Efficacy of live attenuated influenza vaccine in children 6 months to 17 years of age

Abstract

Please cite this paper as: Belshe et al. (2010). Efficacy of live attenuated influenza vaccine in children 6 months to 17 years of age. Influenza and Other Respiratory Viruses 4(3), 141–145. Background It has been suggested that live attenuated influenza vaccine (LAIV) may be less effective in older individuals because of prior wild‐type influenza infections. LAIV is currently approved in the United States, South Korea and Hong Kong for individuals 2–49 years of age. Objective To examine data from previously published pediatric studies to determine the efficacy of LAIV in various age groups. Methods Four studies in which the subject age range exceeded 36 months were identified: one 2‐year study comparing LAIV with placebo and three 1‐year studies comparing LAIV with trivalent inactivated influenza vaccine (TIV). Efficacy against any strain regardless of antigenic similarity to vaccine was analyzed by age; age groups were based on the study design and sample size. A logistic regression model was used to assess whether age, as a continuous variable, was an effect modifier on LAIV efficacy. Results The efficacy of LAIV did not vary with age in children aged 15–84 months compared with placebo or in children aged 6 months to 17 years compared with TIV. Conclusions The available data from prospective, randomized studies in children does not support the concept that prior repeated exposure to influenza, either through wild‐type infection or vaccination with live, attenuated or inactivated vaccines, reduces the efficacy of LAIV compared with placebo or TIV. The decreased immunologic responses to LAIV reported in older individuals or those with pre‐existing immunity do not appear to translate into reduced protection from influenza in children.

Background paper to the recommendation for the preferential use of live-attenuated influenza vaccine in children aged 2–6 years in Germany

“…2b). Age-stratified data from this study were published by Belshe et al [9], showing similar relative efficacy of LAIV vs. TIV in the age groups 6-11 years (31%; 95% CI: −8%-57%; 1376 subjects) and 12-17 years (30%; 95%CI: −43%-66%; 835 subjects), both of which, however, were not statistically significant. Incidences of LRTI were not reported.…”

“…An important question STIKO sought to answer is up to what age LAIV confers better protection against influenza than TIV. In adults, several studies have shown that LAIV provides worse protection than TIV against laboratory-confirmed influenza (see meta-analysis by Belshe et al [9]). This was also observed in a randomized study comparing LAIV, TIV, and placebo in very young adults with a mean age of 23.3 years (range 18-49 years) [18].…”

“…Furthermore, we identified one observational study in children aged 5-18 years [8], which we excluded from further analysis because study participants in the intervention group differed substantially in baseline risk for influenza from those in the comparison group (healthy children were vaccinated with LAIV, children with increased risk of influenza due to an underlying chronic condition were vaccinated with TIV). In addition, we found five publications with meta-analyses and/or subgroup analyses of efficacy and safety data from these three studies and placebo-controlled studies of LAIV [4,9,10,11,12], which we additionally considered in the evidence appraisal process.…”

Urgent challenges in implementing live attenuated influenza vaccine

“…Whilst studies do support the notion that viral shedding and immune response to LAIV may decline upon repeated use 47,48 and with increasing age, 49 this has not yet been correlated to a reduction in vaccine efficacy. 50 Moreover, use of live vaccine on an annual basis is unique to influenza and further study is required to understand the implications. For example, whether subtle changes in antigenicity affect LAIV "take" more than IIV, requiring more frequent strain updates or different methods of strain selection than that established for IIV.…”

Development of high-yield influenza B virus vaccine viruses

“…Since then, two lineages (Victoria, named after B/Victoria/2/1987, and Yamagata, named after B/Yamagata/16/ 1988) can be distinguished genetically and antigenically on the basis of their HA (1,3,4). Until 2000, one of these two lineages tended to dominate each season; however, since 2001 both influenza B virus lineages have been cocirculating in human populations each year (5,6).…”