Second Dose of Influenza Vaccine Offers Greater Protection in Children Under 3 Years: JAMA
Australia: A systematic review and meta-analysis found that two doses of inactivated influenza vaccine provided better protection than a single dose in influenza vaccine–naive children younger than 3 years. However, the additional benefit diminished with age and was not statistically significant when children younger than 9 years were considered. Further high-quality studies are needed to determine the age groups that benefit most from a two-dose vaccination schedule.
The study, published in JAMA Network Open, was conducted by Jessie J. Goldsmith, MSc, from the Department of Infectious Diseases at the University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia, and colleagues.
The World Health Organization (WHO) recommends that children younger than 9 years who have never received an influenza vaccine receive two doses during their first vaccination season, based on evidence from immunogenicity studies. However, the extent to which the second dose improves actual protection against influenza remains uncertain.
To investigate this, the researchers evaluated the additional protection associated with a second influenza vaccine dose in children aged 6 months to younger than 9 years who had no previous influenza vaccination. They searched MEDLINE, EMBASE and CINAHL for relevant peer-reviewed studies published up to March 24, 2025.
The review included studies reporting vaccine efficacy or effectiveness according to the number of doses received. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias. The analysis included 51 studies involving 415,050 participants. The researchers compared vaccine efficacy or effectiveness after one and two doses, examining inactivated influenza vaccines (IIV) and live attenuated influenza vaccines (LAIV) separately.
The analysis revealed the following findings:
- Among children younger than 9 years, receiving a second dose of IIV was associated with an estimated 15-percentage-point increase in vaccine effectiveness. However, the confidence interval ranged from a decrease of 2.8 percentage points to an increase of 33 percentage points, indicating that the difference was not statistically significant.
- In children younger than 3 years, the second IIV dose was associated with a 28-percentage-point increase in vaccine effectiveness, with a 95% confidence interval ranging from 4.7 to 51 percentage points. This improvement was statistically significant.
- The additional protection associated with the second dose appeared to diminish with increasing age, although insufficient data were available to establish the benefit specifically among children aged 3 to younger than 9 years.
- The researchers could not reliably estimate the additional protection provided by a second LAIV dose because too few suitable estimates were available.
The findings suggest that a second dose of inactivated influenza vaccine offers additional protection to vaccine-naive children younger than 3 years, but the benefit was not statistically significant in children younger than 9 years.
The study was limited by few available estimates, small sample sizes, and potential bias in observational studies. The researchers called for high-quality trials and observational studies to determine the benefits of a two-dose schedule across age groups.
Reference:
Goldsmith JJ, Tavlian S, Vu C, et al. Comparison of 2 Doses vs 1 Dose in the First Season Children Are Vaccinated Against Influenza: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2025;8(10):e2535250. doi:10.1001/jamanetworkopen.2025.35250
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