PT  - JOURNAL ARTICLE
AU  - Joseph T. Wu
AU  - Corey M. Peak
AU  - Gabriel M. Leung
AU  - Marc Lipsitch
TI  - Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study
AID  - 10.1101/053421
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 053421
4099  - http://biorxiv.org/content/early/2016/06/16/053421.short
4100  - http://biorxiv.org/content/early/2016/06/16/053421.full
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 vaccines and up to five-fold fractionation with varying efficacy. We consider two allocation scenarios: random 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 5–2 to 7–1 transmission events per infectious individual. Intuition dictates, and we confirm with modeling analysis, that five-fold fractional-doses can dramatically reduce the final epidemic size. If vaccine efficacy is all-or-nothing, as we expect, the conclusion holds that n-fold fractionation is beneficial as long as the efficacy is greater than 1/n. We quantify how the threshold becomes more stringent if fractional vaccines instead provide partial protection to every recipient (i.e. “leaky” vaccine action).Interpretation We conclude that dose fractionation could be a very effective strategy for reducing infection attack rate in populations with a large margin of error in case fractional-dose efficacy turns out to be lower than expected.Funding NIH-MIDAS, HMRS-Hong Kong