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

## TL;DR

This study models how using smaller doses of yellow fever vaccine could help control outbreaks when vaccine supply is limited.

## Contribution

The paper introduces a mathematical model to evaluate the epidemiological benefits of fractional-dose yellow fever vaccination under different efficacy assumptions.

## Key findings

- Fractional dosing could significantly reduce the final size of a yellow fever epidemic if it retains at least moderate efficacy.
- Even with partial efficacy, fractional dosing is beneficial if it immunizes at least 20% of recipients.
- The effectiveness of fractional dosing depends on the vaccine's mode of action and allocation strategies.

## Abstract

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.

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.

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).

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.

NIH-MIDAS, HMRS-Hong Kong