Limited transmission of cervid prions to nonhuman primates provides insights into the zoonotic potential of chronic wasting disease.

Chronic wasting disease (CWD) is an expanding prion disease of cervids. CWD prions persist in the environment, are shed in excreta, and accumulate in tissues of infected cervids, raising concerns about its zoonotic potential. Using cynomolgus macaques, we explored the zoonotic potential of CWD. Although most inoculated macaques remained asymptomatic, sensitive in vitro prion amplification assays revealed low levels of prions in macaque tissues. Inoculation of transgenic mice and bank voles with macaque tissues induced prion disease, achieving 100% transmission rates upon serial passage. One interpretation of these findings is that CWD prions retain infectivity across species and that primate infection may manifest atypically while still enabling transmission. Our results challenge earlier conclusions that minimize the zoonotic risk of CWD and underscore the need for continued surveillance.