The live attenuated vaccine YF17D against yellow fever is one of the most successful vaccines yet developed. In the Journal of Clinical Investigation, Trautmann and colleagues examine baseline immunological parameters that can potentially modulate the efficacy of YF17D. Comparing two populations of YF17D vaccinees, one in Uganda and the other in Switzerland, the authors find higher replication of the attenuated virus in the Swiss cohort; however, this is associated with a more robust neutralizing antibody response and a higher frequency of YF17D-specific CD8+ T cells. The impaired YF17D response in the Ugandan group is associated with across-the-board baseline activation of innate and adaptive immunity, as well as some evidence of immunological exhaustion. The responses of memory T cells and B cells in preimmunized Ugandan subjects also show diminished persistence. These results suggest that preexisting activation of the mmune system can impair the efficacy of YF17D and that boosting, which is not normally recommended by the guidelines of the World Health Organization, may be beneficial to such populations.

J. Clin. Invest. (9 June 2014) doi:10.1172/JCI75429