Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study

Wu, Joseph T.; Peak, Corey M.; Leung, Gabriel M.; Lipsitch, Marc

Our primary analysis shows that dose fractionation of YF vaccine, if there is no loss of efficacy as currently assumed, could provide a substantial benefit to reducing the attack rate of YF in a population. We consider this assumption of full efficacy for five-fold fractionation to be the most likely scenario, despite the lack of efficacy data on any YF vaccine, for several reasons: 1) two studies of five-or greater-fold vaccination doses have shown indistinguishable immunogenicity in humans; 2) at least some preparations of YF vaccine substantially exceed the WHO minimum standard for potency of 1,000 IU/dose, so fractionation at some level could be performed without dropping below that threshold; 3) YF vaccine is live attenuated virus, so a biological rationale exists that if a productive vaccinevirus infection can be established by a fractionated dose, protection should be comparable to that with a higher dose. Nonetheless, to assess the robustness of the conclusion that dose fractionation is likely to be beneficial, against the possibility that in fact efficacy of fractionated doses is lower than anticipated, we consider the possibility that five-fold fractionated dosing fails to immunize a proportion (1−VE(5)) of recipients. We find that as long as at least 20% of recipients are fully immunized by the vaccine, more people would be immunized by vaccinating five times as many people with one-fifth the dose, and so the population-wide benefits of higher coverage would outweigh the lower efficacy of fractionated dosing for individual vaccinees.