A randomized trial in Kenya and Uganda finds that infants who receive a lower dose of yellow fever vaccine have lower antibody levels against the mosquito-borne disease than those given the standard dose, suggesting that minimum-dose requirements for adults aren’t generalizable to infants.
For the double-blind non-inferiority trial, published yesterday in The Lancet, researchers randomly assigned 420 infants 9 to 12 months old to receive either the standard dose (more than 13,000 IU [international units]) or 500 IU of the live attenuated yellow fever vaccine from October 2021 to June 2023.
The primary outcome was seroconversion, defined as a fourfold or greater increase in antibody levels, 28 days after vaccination. Non-inferiority was shown if the lower bound of the 95% confidence interval for the difference in seroconversion rates exceeded −10 percentage points.
Yellow fever vaccine production is limited by its culture in eggs and cannot rapidly be scaled up in response to outbreaks.
The World Health Organization (WHO) “recommends fractional dose vaccination to address yellow fever vaccine shortages during outbreaks,” the study authors wrote. “In adults, a 500 IU dose has recently been shown to be non-inferior to the full standard dose, but the minimum effective dose for children is unknown.”
Correlate of protection unknown
At 28 days, the seroconversion rate was 99% for the standard dose and 93% for the 500-IU dose in the per-protocol population. The difference in seroconversion rates was −6.15 percentage points, which didn’t meet the non-inferiority threshold. Twelve serious adverse events were reported; all were considered unrelated to the vaccine.
