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

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

We assume that vaccine action is all-or-nothing, i.e. n-fold fractional-dose vaccines provide 100% protection against infection in a proportion VE(n) of vaccinees and no protection in the remainder. In this case, n-fold dose fractionation results in lower IAR if and only if the vaccine efficacy of n-fold fractional-dose vaccines is at least 1/n times that of standard-dose vaccines, i.e. VE(n) > VE(1) / n (see appendix for details). We term this the benefit threshold for dose fractionation. We also consider the alternative case in which vaccine action is leaky, i.e. n-fold fractional-dose vaccines reduce the hazard of infection (the probability of disease transmission per mosquito bite) of each vaccinee by a proportion VE(n). 22, 23 Compared to all-or-nothing vaccines, leaky vaccines have substantially higher benefit thresholds, especially when transmissibility is high (see Results). However, YF vaccine action is much more likely to be all-or-nothing than leaky (see Discussion). As such, we present our main results in the context of all-or-nothing vaccine action. In principle, disease transmission can be halted if the effective vaccine coverage, defined as the proportion of population immunized (e.g.V × n × VE(n) if vaccination comprises n-fold fractional-dose vaccines only), exceeds the herd immunity threshold 1 − 1/R 0 .