Abstract
IMPORTANCE: Based on the findings of immunogenicity studies, the World Health Organization has recommended influenza vaccine-naive children younger than 9 years receive 2 doses of influenza vaccine in the first year of vaccination. OBJECTIVE: To estimate the increase in protection associated with the second dose of influenza vaccine for influenza vaccine-naive children younger than 9 years. DATA SOURCES: MEDLINE, EMBASE, and CINAHL were searched for articles published from inception to March 24, 2025. STUDY SELECTION: Peer-reviewed studies that reported vaccine efficacy or vaccine effectiveness against influenza for influenza vaccine-naive children aged 6 months to younger than 9 years by dose number were included. Modeling and cost-effectiveness studies were excluded. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened and extracted data and assessed studies' risk of bias. The study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. MAIN OUTCOMES AND MEASURES: For studies reporting both 1 and 2 dose estimates, the difference in vaccine efficacy or effectiveness was calculated in order to estimate the additional protection associated with the second dose. Pooled vaccine efficacy or effectiveness and difference were calculated separately for inactivated influenza and live attenuated influenza vaccines. RESULTS: There were 51 studies with 415 050 participants included in this analysis. The pooled absolute increase in vaccine effectiveness of a second inactivated influenza vaccine dose in the first year of vaccination was 15 percentage points (pp) (95% CI, -2.8 pp to 33 pp) for those younger than 9 years and 28 pp (95% CI, 4.7 pp to 51 pp) for children younger than 3 years. Insufficient estimates were available to assess the incremental benefit associated with a second dose of live attenuated influenza vaccine. CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of influenza vaccine efficacy and effectiveness in the first year of vaccination, receiving 2 doses of inactivated influenza vaccine was associated with improved protection for children younger than 3 years compared with those who receive one dose; however, when the age range was broadened to younger than 9 years, the second dose of inactivated influenza vaccine was not significantly associated with increased protection. Additional high-quality studies are needed to assess the impact of the 2-dose schedule for both vaccine types by age to determine the age range for which a 2-dose schedule is beneficial.