For children who have never been vaccinated against the flu, receiving two doses of the inactivated flu vaccine significantly enhances protection compared to a single dose, particularly in those younger than three years. This finding emerges from a systematic review and meta-analysis published in JAMA Network Open.
The study, led by Jessie Goldsmith, a PhD student at the University of Melbourne’s Doherty Institute, analyzed data from 51 studies involving over 400,000 participants. The research revealed that the pooled absolute increase in vaccine effectiveness of a second inactivated flu vaccine dose during the first year of vaccination was 15 percentage points for children under nine years and 28 percentage points for those under three years.
Key Findings and Statistics
In 12 studies focusing on real-world vaccine effectiveness, vaccine-naive children under nine years old who received one dose showed a pooled vaccine effectiveness of 35% against any flu strain. This effectiveness increased to 43% with two doses. Five studies comparing one- and two-dose estimates demonstrated pooled vaccine effectiveness rates of 31% and 43%, respectively, with a 15 percentage point increase in effectiveness.
“Among children younger than three years, the combined vaccine effectiveness for one dose was 14%, while two doses increased effectiveness to 41%, marking a 28 percentage point rise,” the study reported.
Further analysis of five studies on vaccine efficacy found that the pooled two-dose vaccine efficacy was 52% in children younger than nine years and 51% in those younger than three years.
Expert Opinions and Recommendations
Goldsmith emphasized the importance of the second dose, particularly for children under three. “For inactivated vaccine effectiveness studies, the benefit of the second dose in the first year of vaccination against influenza is more definitive when the studies were limited to children under three compared with the broader age group of children younger than nine years,” she stated in an interview with MedPage Today.
The World Health Organization (WHO) recommends that children younger than nine years who have not previously received a flu vaccine should start with two doses, spaced at least four weeks apart, followed by one dose annually. This recommendation is echoed by the American Academy of Pediatrics.
Understanding the Age-Related Differences
The study explored the reasons behind the differing vaccine effectiveness in younger versus older children. Goldsmith pointed out two primary factors: the development of the immune system and previous exposure to the influenza virus. “Their immune system has had the opportunity to develop further, and they are more likely to have been exposed to the influenza virus,” she explained.
However, the study noted a lack of sufficient data to compare the one-dose and two-dose approaches with the live attenuated influenza vaccine, recommended for children aged two years and older. Seven trials indicated that pooled vaccine efficacy against any flu strain was 51% for one dose and 82% for two doses.
Research Methodology and Limitations
Goldsmith and her team conducted this systematic review and meta-analysis using trusted databases such as Medline, Embase, and CINAHL, covering studies from inception to March 2025. They included 51 studies with 415,050 participants, conducting separate analyses for inactivated and live attenuated flu vaccines due to their different starting ages.
Despite these comprehensive efforts, the study faced limitations, including a small number of available estimates and high levels of uncertainty in those estimates. Insufficient data also precluded a separate analysis of the impact of two doses on children aged three to nine years.
As the flu season approaches, these findings underscore the importance of adhering to vaccination guidelines, particularly for young children, to enhance their protection against influenza.
