When Should Fractional-dose Vaccines be Used?

Problem definition: Vaccination campaigns often face significant operational challenges such as limited stockpiles, vaccine delivery delays, and constrained administration capacity. In such contexts, fractional-dose vaccines have been described in the medical literature as a possible strategy because their efficacy reduction is typically not commensurate with the level of fractionation, allowing greater population coverage. We seek to determine the optimal use and potential benefits of a fractionated vaccine dose with lower and more uncertain efficacy, given the specific supply constraints faced by a country. Methodology/results: We employ a susceptible-infected-recovered (SIR) epidemic model integrating vaccination with full and fractional doses over time. We embed it within a deterministic optimal control model aimed at identifying vaccination policies that minimize total infections during an epidemic, given operational constraints restricting the stockpile, delivery rate, and administration of vaccines. Using a statistical approach described in the clinical literature for estimating the uncertainty around fractional-dose efficacy, we conduct two application case studies grounded in real-world scenarios. Our theoretical analysis provides an intuitive characterization of the optimal vaccination policy that, depending on the epidemic and operational parameters, may utilize a combination of full- and fractional-dose vaccines, either simultaneously or sequentially. We also examine simpler policies that employ a single vaccine dosage throughout the epidemic. We conclude that, although these single-dose policies can often be almost as effective as the optimal policy in averting infections, they are not as robust to the uncertainty affecting fractional-dose vaccine efficacy. Managerial implications: Fractional-dose vaccines, used either alone or in conjunction with full-dose vaccines, present an opportunity to significantly reduce infections during an epidemic in resource-constrained settings. The proportion of fractional-dose vaccines relative to full-dose vaccines in a campaign should generally increase with the maximum vaccine administration rate and decrease with the total antigen stockpile available.