In all age groups studied, LAIV and TIV were effective in preventing influenza illness. In children, all four comparative studies of LAIV and TIV demonstrated that LAIV was more protective against culture-confirmed influenza illness in children 6 months to 17 years of age.2,3,5,7
These results are supported by the results of studies that have compared the vaccines to placebo. A meta-analysis of six placebo-controlled studies of LAIV calculated that the mean efficacy of two doses against matched strains of all subtypes in previously unvaccinated young children was 77% (95% CI: 72, 80)27
; the mean efficacy of 1 dose of LAIV in previously vaccinated children was 87% (95% CI: 81, 90).27
Three separate meta-analyses of the efficacy of TIV against laboratory-confirmed influenza in children compared with placebo calculated that the mean efficacy of TIV against matched strains was 59% (95% CI: 41, 71),28
63% (95% CI: 45, 70),29
and 65% (95% CI: 45, 77).30
Studies also indicate that the efficacy difference between LAIV and TIV in children increases with circulation of antigenically mismatched strains. As noted previously, LAIV is approved for eligible children 2–17 years of age because of an observed increased rate of medically attended wheezing in children 6–23 months of age.
In contrast, most comparative studies in individuals 17–49 years of age have demonstrated that LAIV and TIV were similarly efficacious or that TIV was more efficacious. A randomized, culture-confirmed field trial conducted during three influenza seasons demonstrated that TIV was more efficacious than LAIV in healthy adults,10–12
with a statistically significant difference demonstrated in 2007–2008.10
Retrospective effectiveness studies of influenza-like illness in the US military have demonstrated similar results in their overall population.13
However, in the US military studies, LAIV was more protective than TIV against influenza-like illness in new recruits of all ages and similarly effective in older non-recruits.14
Additionally, studies conducted in 1997–1998 suggested that LAIV was more protective against the circulating mismatched A/H3N2 strain.15,16
Among individuals 17–49 years of age, the relative efficacy of LAIV and TIV appear to vary depending on the specific population studied, the type of study, and the degree of antigenic match between the study vaccines and circulating strains. Among adults ≥60 years of age, the limited available data suggest that the two vaccines are similarly effective. However, as noted previously, because of limited data, LAIV is not currently approved in the United States in adults ≥50 years of age.
Both LAIV and TIV can induce priming immune responses and boost pre-existing anti-influenza immunity. However, LAIV appears to be more effective than TIV as a priming vaccine, and TIV appears to be more effective in boosting pre-existing immunity.31,32
Given the annual changes in circulating strains of influenza, both types of immune responses are important for individuals of all ages. However, these differential mechanisms of action may explain the differential relative efficacy of LAIV and TIV in children and young adults. TIV efficacy may be higher in adult versus pediatric populations because adults have greater immunologic priming from multiple previous natural infections with influenza. Conversely, it has been suggested that LAIV efficacy may decline in adults because higher pre-existing anti-influenza immunity may limit intranasal replication of LAIV.10,11
However, an analysis of multiple efficacy studies conducted in children 6 months to 17 years of age found no evidence of a decline in LAIV efficacy with increased age or with increased pre-existing immunity to influenza within this age range.4
In adults, no evidence has been published to directly support this hypothesis; post hoc analyses of completed studies in adults should be conducted to examine this issue.
Variations in the severity of the influenza illness measured in a study may influence relative efficacy estimates. As noted earlier and in the , studies have demonstrated that LAIV-vaccinated children and adults who develop influenza illness tend to have less severe illness than TIV-vaccinated individuals, perhaps because of enhanced mucosal or cellular immunity. As a result, the relative efficacy of LAIV versus TIV in children and adults may increase when measured against more severe illness. The impact of breakthrough illness severity on LAIV and TIV efficacy should be evaluated in future studies and through post hoc analyses of completed studies.
The primary limitation of the current analysis is the small number of prospective, randomized studies. Influenza vaccine efficacy studies that are appropriately powered to compare two effective vaccines require large numbers of subjects and are very costly. As a result, it is not surprising that few have been conducted. Additionally, given the annual variation in both circulating strains and the influenza attack rate, consistent results across multiple seasons and geographies are needed for robust conclusions. In children, particularly younger children, multiple randomized and observational studies as well as meta-analyses of placebo-controlled studies have yielded consistent results. In adults, less data are available and results have been more variable. To more fully understand the relative benefits of TIV and LAIV in adults, additional research is needed. A multi-country, multi-year, double-blind, well-powered study in individuals ≥18 years of age would be valuable. Additional studies in older children and adolescents would also be valuable. These studies should be stratified so that relative efficacy can be determined by age group. Multiple aspects of baseline anti-influenza immunity should be evaluated to elucidate the role of pre-existing immunity, and various influenza symptoms should be collected to describe the impact of LAIV and TIV on influenza illness of varying severity.