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

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

suggesting that efficacy should be nearly equivalent to that for full doses. This was 645 confirmed by the analysis of peak viremia, which was equivalent for standard dose and for 646 doses down to 11% of the full dose (9-fold fractionation). It was further confirmed by peak 647 cytokine responses, which were comparable to the standard dose for all cytokines tested, 648 down to at least a 9-fold fractional dose. For even lower doses, the proportion 649 seroconverting after vaccination was lower than the 97% observed for the full dose, but the 650 antibody response among the seroconverters appears to be similar at all doses. 9 These data 651 collectively suggest that down to approximately 9-fold fractional dosing of this vaccine the 652 response should be equivalent, and that for further fractionation there may be a failure to 653 induce any substantial response in a fraction of recipients, but the neutralizing antibody 654 titres in those who do respond should be comparable. This pattern is consistent with an all-655 or-nothing model. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.