A fifth of a yellow fever dose protected toddlers as well as a full one

Giving young children one-fifth or one-half of the standard yellow fever vaccine dose produced initial immunity no worse than a full dose, according to a randomised trial of 1,784 Ugandan toddlers [s1]. The finding matters because yellow fever vaccine is periodically in short supply during outbreaks, and stretching each vial further — "dose-sparing" — could let a fixed stock protect several times as many people, but the evidence that it works in children under two had been missing until now [s1].

Yellow fever is a mosquito-borne viral disease that still causes large outbreaks in parts of Africa and South America, including the continuing alerts across the Americas in 2026. A single dose of the live-attenuated vaccine gives long-lasting protection, and fractional doses had already been shown to be safe and immunogenic in adults and older children — the approach the World Health Organization endorsed for emergency campaigns during the 2016 supply crisis in Angola and the Democratic Republic of the Congo. What remained untested was whether the same held for the youngest children, whose immune systems respond differently and who are a core target of routine immunisation [s1].

What the trial did

The study was a phase 4, single-blind, randomised trial run at three public-sector health facilities in Kampala, Uganda [s1]. It enrolled children aged 9 to 23 months with no history of yellow fever or prior vaccination, grouped into three age strata and randomly assigned in equal numbers to receive one-fifth (0.1 mL), one-half (0.25 mL) or a full (0.5 mL) dose of the 17DD yellow fever vaccine [s1]. Between March 2019 and May 2021, 1,784 children were randomised — 600 to the one-fifth dose, 594 to the one-half dose and 590 to the full dose — with a median age of 13 months [s1][s2]. Their immunity was measured four weeks after vaccination using a plaque-reduction neutralisation test, the standard laboratory assay for protective yellow fever antibodies [s1].

The primary question was framed as non-inferiority: the trial asked not whether the fractional doses were better, but whether their seroconversion rate fell short of the full dose by no more than a prespecified margin of 5 percentage points [s1]. Both fractional doses cleared that bar. There was no difference in seroconversion between the one-fifth dose and the full dose, and the difference between the one-half dose and the full dose was −0.17 (95% confidence interval, −0.52 to 0.17) — comfortably inside the non-inferiority margin [s1]. In plain terms, one-fifth of a dose generated the same initial protective antibody response as a full dose in this age group [s1].

Why "non-inferiority" and "initial" are load-bearing words

Two qualifiers deserve emphasis, because dose-sparing claims are easy to overstate. First, this was a non-inferiority trial: it is built to show a fractional dose is not meaningfully worse on a single measure, not to show it is equivalent in every respect. The result licenses using less vaccine in a shortage; it is not an argument that the full dose is wasteful under normal supply [s1].

Second, the primary endpoint captured immunity four weeks after vaccination — the initial seroconversion [s1]. Yellow fever protection is expected to last for decades, and the trial followed children out to one year and then to between 13 and 48 months to look at durability [s1]. The headline result is about whether protection is established, not yet the full picture of how long a fractional dose sustains it in very young children — the question that matters most for a vaccine meant to protect for life, and the one to watch as the longer-term data are reported.

What it changes

The practical payoff is in outbreak response. When demand for yellow fever vaccine outstrips the global stockpile, the choice can be between vaccinating some people fully and reaching a much larger population with fractional doses to blunt an epidemic. Extending the evidence base to children aged 9 to 23 months — a group central to both routine schedules and emergency campaigns — removes one of the gaps that made health authorities cautious about applying dose-sparing across the board [s1]. The trial was funded by the US Centers for Disease Control and Prevention rather than a vaccine manufacturer, and its authors conclude the results "support the use of fractional dose yellow fever vaccines among young children for outbreak response during supply shortages" [s1].

That is a carefully bounded claim: a tool for emergencies and shortages, backed now by trial data in the age group where it was previously untested [s1]. This article describes trial findings and is not medical advice.

Sources

• Immunogenicity of fractional one-fifth and one-half doses of 17DD yellow fever vaccine in children aged 9–23 months in Uganda — The Lancet, published online September 2026
• Fractional Doses of Yellow Fever Vaccine in Children, trial registration (NCT03725618) — ClinicalTrials.gov