vaccinationHistorical reports on outbreaks of variola major offer insightto the use of post-exposure vaccination as a medical countermea-sure to OPXV exposure. As early as 1904, it was well known thatvaccination of persons exposed to smallpox helped protect thesepersons from smallpox disease [30], but the literature is rife withconflicting information about the timing of effective post-exposurevaccination. A summary review of the epidemiological literaturewhich specifically mentions post-exposure vaccination efficacy inthe context of variola major outbreaks [31–42] highlights historicestimations of the efficacy of vaccination at various timepointspost-exposure (Table 1). This literature is complicated to inter-pret due to various data gaps, which have also been detailed inTable