Low-dose yellow fever vaccination in infants: a randomised, double-blind, non-inferiority trial

Journal article

Background: The World Health Organization recommends fractional dose vaccination to address Yellow Fever (YF) vaccine shortages during outbreaks. In adults, a 500 IU dose has recently been shown to be non-inferior to the full standard dose, but the minimum dose for children is unknown.

Methods: We conducted a randomised, double-blind, non-inferiority trial in Kenya and Uganda, involving infants aged 9–12 months old with no prior YF vaccination or infection. Participants were randomly assigned 1:1 in blocks of variable sizes of 4, 6 or 8 to receive either the standard dose (>13,000 IU) or 500 IU of the Institut Pasteur de Dakar 17D-204 YF vaccine, co-administered with measles-rubella (MR) vaccine. The primary outcome was seroconversion 28 days post-vaccination, defined as a four-fold or greater increase in antibody titre at day 28 from the baseline (day 0), as measured by the 50% plaque reduction neutralisation test (PRNT50). Non-inferiority was shown if the lower bound of the 95% confidence interval (CI) for the difference in seroconversion rates between doses exceeded −10 percentage points. This study is registered with ClinicalTrials.gov, NCT04059471.

Findings: Between Oct 7, 2021, and Jun 14, 2023, 420 infants were enrolled and randomised (210 participants in each group). The seroconversion rate at day 28 was 99% (95% CI 96 to 100; 177 of 179 infants) for the standard dose and 93% (95% CI 88 to 96; 166 of 179 infants) for the 500 IU dose in the per-protocol population. The difference in seroconversion rate was −6.15 percentage points (95% CI −10.27 to −2.02). Twelve serious adverse events were reported in the study (8 in the 500 IU dose group and 4 in the standard dose group) but all were unrelated to vaccination.

Interpretation: When compared to the full YF vaccine dose, a dose of 500 IU did not meet the noninferiority criterion suggesting that minimum dose requirements in adults are not generalisable to infants.

Authors: Kimathi, D; Juan-Giner, A; Bob, NS; Bejon, P; Warimwe, G

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Lancet
• Volume: 407
• Issue: 10527
• Pages: 497-504
• Publication date: 2026-01-13
• Acceptance date: 2025-10-09
• DOI: 10.1016/S0140-6736(25)02069-0
• EISSN: 1474-547X
• ISSN: 0140-6736
• Language: English
• Keywords: FFR