Abstract
OBJECTIVES: Concerns regarding the misuse of the variola virus for bioterrorism and its re-emergence still prevail. The possibility of orthopoxvirus infection and epidemics in humans also exists, including the variola and monkeypox viruses. The latter causes mpox and has posed a global risk since 2022. Accordingly, there is an increasing need for research and development of vaccines and therapeutics for orthopoxviruses, driven by pathological understanding of their infection mechanism, including vaccinia and animal models of orthopoxviral infections. This study introduces methods for establishing animal models of orthopoxvirus-related infections and the pathological characteristics of these models. METHODS: Establishing animal models of orthopoxvirus infection was based on their pathological characteristics through reviews of related articles and examples of efficacy evaluations of vaccinia immunoglobulins and therapeutic monoclonal antibodies for the treatment of vaccinia virus infection using animal models of orthopoxvirus infections. RESULTS: Animal models of orthopoxvirus infection show various pathological aspects depending on the immune status and infection route, having been used in nonclinical trials or animal experiments to evaluate the efficacy of smallpox vaccines and therapeutic candidates. Monoclonal antibodies show potential to replace existing vaccinia immunoglobulins. CONCLUSIONS: Animal models of orthopoxvirus-associated infection can improve our pathological understanding of orthopoxviral infections and be used to evaluate the efficacy of candidates in the development of vaccines and therapeutics for smallpox and orthopoxvirus-associated infections.