Historical reports on outbreaks of variola major offer insight to the use of post-exposure vaccination as a medical countermea-sure to OPXV exposure. As early as 1904, it was well known that vaccination of persons exposed to smallpox helped protect these persons from smallpox disease [30], but the literature is rife with conflicting information about the timing of effective post-exposure vaccination. A summary review of the epidemiological literature which specifically mentions post-exposure vaccination efficacy in the context of variola major outbreaks [31–42] highlights historic estimations of the efficacy of vaccination at various timepoints post-exposure (Table 1). This literature is complicated to inter-pret due to various data gaps, which have also been detailed inTable