Medical countermeasures to OPXVs are important because smallpox reemergence through a release of VARV would be a highconsequence event (although the risk of this happening is perceivedto be low), and because emerging and reemerging zoonotic OPXV-associated diseases continue to be a public health issue. The WHOCommission to Certify Smallpox Eradication instituted an interna-tional surveillance program for smallpox-like diseases in 1971 [16],which ultimately resulted in an increased awareness of humanmonkeypox virus (MPXV) infection [17]. Today, MPXV infectionsare on the rise in the Democratic Republic of the Congo (DRC)[18], and outbreaks in Sudan and the United States indicate thepotential for MPXV to spread [19]. Other OPXV infection outbreaksare routinely observed and include VACV in Brazil [20], CPXV inEurope [21], and buffalopox in India [22]. Current research alsoindicates that OPXV in wildlife reservoirs is more prevalent thanpreviously thought [23–25]. Lastly, long-held concerns regardingthe threat of smallpox as a weapon of bioterrorism increased afterthe events of September 11, 2001 and the subsequent anthraxreleases [26]. Combined, these conditions make the developmentof medical countermeasures against OPXV-associated disease anongoing and current research effort.