The recent Ebola virus epidemic was waning by the time stakeholders were ready to field vaccines for testing but an evidence-based response to a novel pathogen will surely be required again. Here, we present a design for such a randomized controlled trial. The permuted locus trial was originally intended for studying the influence of water wells on trachoma. While outcomes can be measured in individuals, neither individuals nor groups are themselves randomized to arms, just potential well-sites, or in the case of an epidemic, index cases. The permuted locus trial may be used when classic individual and cluster-randomized trial design and analyses may not be optimal.