The global demand for yellow fever vaccine has surpassed supply following large urban outbreaks in Africa in 2016 and the threat of urban transmission in Brazil. As a dose-sparing strategy, the World Health Organization (WHO) has recommended the use of a fractional dose of the yellow fever vaccine in emergency settings, while calling for clinical trials to investigate this alternative vaccination strategy. Subsequently, Dr. Cummings and others are serving as consultants on a Phase IV safety and non-inferiority trial led by Epicentre-Medecins Sans Frontieres. This trial, conducted in two sites in sub-Saharan Africa, will assess non-inferiority in seroconversion among participants receiving a one-fifth fractional dose compared to full dose for each WHO-prequalified vaccine. Sub-studies in children and HIV-positive adults are planned, pending results from the primary study in healthy adults.