KAMPALA, September 13 — A clinical trial in Uganda has found that a one-fifth dose of yellow fever vaccine protected children under age 2 as well as the full dose, a result that could stretch scarce vaccine supplies during outbreaks. The study, published in The Lancet Global Health in 2024, enrolled 1,784 children under 2 years old in Uganda. Participants received the vaccine at full strength, half strength, or one-fifth strength.
The fractional dose generated an immune response that was non-inferior to the full dose, meaning it protected at least as well. The trial was conducted by researchers from the Uganda Virus Research Institute (UVRI) and the London School of Hygiene & Tropical Medicine (LSHTM), among other institutions.
The work was funded by the Wellcome Trust and other partners. The authors declare no conflicts of interest.
Why this matters for outbreak response
Yellow fever is a viral hemorrhagic disease transmitted by mosquitoes, endemic in tropical regions of Africa and South America. The World Health Organization estimates that yellow fever causes 200,000 cases and 30,000 deaths worldwide each year, with 90% of cases occurring in Africa. There is no specific antiviral treatment; vaccination is the primary prevention method.
The current global supply of yellow fever vaccine is limited, with only a handful of manufacturers. In 2016, during yellow fever outbreaks in Angola and the Democratic Republic of the Congo, WHO recommended fractional dosing as an emergency measure to stretch supplies.
That recommendation was based on earlier studies in adults showing that fractional doses were immunogenic. However, data on fractional dosing in children under 2 were lacking. The Uganda trial addresses this gap.
The study’s findings support the use of fractional dosing in children during outbreaks, potentially allowing health authorities to vaccinate five times as many people with the same amount of vaccine. The full dose is 0.5 mL; the one-fifth dose is 0.1 mL.
A vaccine with deep roots
The standard yellow fever vaccine has been used since the 1930s. The live attenuated vaccine strain 17D was developed in 1937 by Max Theiler and colleagues at the Rockefeller Foundation. The trial’s design was a randomized, double-blind, controlled study.
The results showed that the fractional dose was safe and immunogenic. The study’s limitations include the lack of long-term follow-up data.
Further research is needed to assess the duration of protection from fractional dosing. The WHO’s Strategic Advisory Group of Experts (SAGE) on Immunization has previously reviewed fractional dosing and recommended it for outbreak response in adults. The new data may inform future recommendations for children.
The WHO has not yet updated its recommendations based on this trial. The findings are expected to be reviewed by WHO’s SAGE.
The trial’s results are consistent with previous studies in adults. The findings could have significant implications for vaccine supply and outbreak response in Africa and beyond. Consult your doctor for medical advice.
