Although both pre-exposure vaccination and post-exposureantiviral therapy studies in surrogate models contribute to ourunderstanding of outcomes following OPXV challenge, for the pur-poses of this review, only those surrogate model studies that haveprovided information regarding the efficacy of post-exposure vac-cination are addressed. The data from these few reports are highlyvariable depending on the surrogate model used. In contrast tothe human epidemiologic literature, where “post-exposure” maynot necessarily mean post-infection, in the animal models, allpost-exposure data on vaccine efficacy is “post-infection”. Studiesthat did not show a significant survival benefit for post-exposurevaccination include a study where 2.5 × 105TCID50of VACV-Elstree (intracutaneous) was administered 1 day post-exposure incynomologous macaques infected with 107pfu of MPXV (intratra-cheal) without any significant survival benefit when compared tocontrol animals [49]. In a second study, 106pfu of Elstree (scarifica-tion) or 108IU of Modified Vaccinia Ankara (MVA) (intramuscular)were administered post-exposure to BALB/C mice which were chal-lenged with 104or 106pfu (VACV-Western Reserve) (respiratory)respectively. The authors report that although MVA administra-tion within 3 h of challenge protected the mice from death, theseanimals still manifest substantial disease symptoms. There wasno significant survival benefit with MVA vaccination on day 1, 2,