RT Journal Article SR Electronic T1 Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study JF bioRxiv FD Cold Spring Harbor Laboratory SP 053421 DO 10.1101/053421 A1 Joseph T. Wu A1 Corey M. Peak A1 Gabriel M. Leung A1 Marc Lipsitch YR 2016 UL http://biorxiv.org/content/early/2016/05/14/053421.abstract AB Background The ongoing yellow fever (YF) epidemic in Angola is placing strain on the global vaccine supply. In order to extend vaccine supply and reduce the cost of mass-vaccination, dose sparing by fractional-dose vaccination has received heightened consideration. Five-fold fractionation is similar to the standard dose in safety and immunogenicity. However, no YF vaccine efficacy trials have been performed in humans, so it is possible that fractional-dose vaccines may be less efficacious even if equally immunogenic. There is an urgent need to study under what conditions fractional dosing could provide epidemiologic benefits in reducing transmission.Methods We estimated the effective reproductive number for YF in Angola using disease natural history and case report data. Using these results and simple mathematical models of YF transmission, we calculated the expected final size of an epidemic under varying levels of vaccine coverage with standard-dose vaccine and up to five-fold fractionation with varying efficacy. We consider three allocation scenarios: random; targeted at only susceptible individuals; and whereby children receive standard-dose vaccines while adults receive fractional-dose vaccines.Findings The effective reproductive number early in the outbreak ranged from approximately 5 to 12 transmission events per infectious individual. As expected, if five-fold fractional-doses retain 100% efficacy, the final epidemic is dramatically reduced, especially if standard-dose vaccine coverage is near 20%. If instead some fractional-dose recipients do not become immunized, the five-fold fractional-dose strategy is always beneficial, as long as this dose produces immunity in at least 20% of recipients. We quantify how the threshold becomes more stringent if vaccine action is leaky.Interpretation We conclude that dose fractionation could be a very effective strategy for improving coverage of YF vaccines and reducing infection attack rate in populations, possibly by a large absolute and relative margin, if high to moderate efficacy is maintained by reduced-dose formulations.Funding NIH-MIDAS, HMRS-Hong Kong