Receiving two doses of inactivated influenza vaccine is associated with improved protection against flu for vaccine-naive children younger than 3 years of age, according to a new study published in JAMA Network Open (2025;8[10]:e2535250).

The systematic review and meta-analysis found that although two doses conferred clear benefits in this youngest age group, the added protection diminished among older children.

“Our study supports the two-dose schedule recommended by the World Health Organization for children that have not been vaccinated against influenza previously,” said Jessie J. Goldsmith, MSc, an epidemiology research fellow in the Department of Infectious Diseases and the Peter Doherty Institute for Infection and Immunity at the University of Melbourne, in Australia.

2 Shots for the Youngest

The publication analyzed 51 studies encompassing more than 415,000 participants to determine whether two doses in the first year of vaccination provided additional protection compared with one.

For children younger than 3 years of age, a second dose of the inactivated influenza vaccine increased vaccine effectiveness by 28 percentage points compared with a single dose. However, when the analysis was expanded to include children up to age 9, the increase dropped to 15 percentage points and was not statistically significant.

Would Older Children Benefit From 2 Shots?

Ms. Goldsmith emphasized the need for more rigorous research in older children.

“Many of the /existing studies aiming to assess the impact of influenza vaccination by dose on previously unvaccinated children were at a high risk of bias,” she said. “Given that evidence for children aged 3 to less than 9 is limited, more studies are needed that include this older age group. When those future studies try to assess the impact of a second dose, they should carefully consider their classification of the doses received.”

Ms. Goldsmith reported no relevant financial disclosures.