Design: phase 4, single-blind, randomised, 1:1:1 non-inferiority trial at three public-sector facilities in Uganda
Population: 1,784 children aged 9–23 months with no history of yellow fever disease or vaccination; median age 13 months
Primary outcome: seroconversion at 4 weeks by 50% plaque reduction neutralisation test, 5 percentage-point non-inferiority margin
Effect: half dose vs full −0.17 percentage points (95% CI −0.52 to 0.17); no difference between one-fifth and full

Fractional dosing stretches a limited vaccine supply across an outbreak, and it was already supported in adults and older children. The missing group was children under two, who are both a priority for routine yellow fever immunisation and the group in whom immune responses are least predictable.

This phase 4 trial in Kampala randomised 1,784 children aged 9–23 months, in three age strata, to one-fifth (0.1 mL), one-half (0.25 mL) or full (0.5 mL) doses of 17DD yellow fever vaccine. Seroconversion at four weeks, by 50% plaque reduction neutralisation test, was the primary endpoint, with a non-inferiority margin of 5 percentage points. Both fractional doses met it — the one-half dose differed from full by −0.17 percentage points (95% CI −0.52 to 0.17), and there was no difference between one-fifth and full.

The result is about outbreak response, not routine schedules. Seroconversion at four weeks is an immunological endpoint, and the trial followed participants to one year and beyond for exactly the reason that matters: whether a fractional dose gives durable protection is a different question from whether it seroconverts.

This supports fractional dosing during documented supply shortages, not a change to routine immunisation schedules.
The endpoint is seroconversion, not protection against yellow fever disease.
Yellow fever is not endemic in India, but the certificate requirement for travellers from endemic areas makes supply and dosing policy relevant to travel clinics.
Fractional dosing needs reliable small-volume administration — the technique is part of what is being adopted, not just the policy.

Why it matters

During an outbreak, a fifth-dose policy turns one vial into five children, and the under-twos were the group that policy could not previously include.

The statistics, in plain English

A non-inferiority margin of 5 percentage points means the trial set out to rule out a fractional dose being worse by more than that — and the half dose came in at −0.17 with an interval no wider than about half a percentage point either way, which is a far tighter result than the margin required. Note the primary analysis was per protocol, which in a non-inferiority trial tends to favour the non-inferiority conclusion; an intention-to-treat analysis was also done.