The LVD/NIAID/NIH MVA1974 clone as an Mpox vaccine - preclinical assessment upon in a model of lethal infection with Orthopoxvirus monkeypox in mice.

Monkeypox virus (MPXV), a genetically distinct member of the Orthopoxvirus genus, causes a febrile vesicular illness in humans and animals, recently renamed Mpox. In 2022, Mpox cases were reported in 115 non-endemic countries, prompting the World Health Organization (WHO) to declare a Public Health Emergency of International Concern. A resurgence of cases in August 2024, centered in the Democratic Republic of Congo and neighboring regions, led to renewed international concern. The Modified Vaccinia Ankara (MVA) virus, originally developed as a safer smallpox vaccine, has demonstrated protective efficacy against MPXV. However, only a limited number of MVA clones have been evaluated or produced specifically for Mpox prevention. In this study, we assessed the immunogenicity and protective efficacy of the LVD/NIAID/NIH MVA1974 clone-previously untested for Mpox-in a mouse model. Mice were immunized intramuscularly with 1 × 108 FFU of the MVA1974 virus using a prime-boost regimen. Immunization induced robust immune responses and provided complete (100 %) protection against a lethal MPXV challenge. Given the current shortage of approved MVA-based vaccines amid growing global demand, alternative MVA clones such as MVA1974 represent promising candidates for further development as Mpox vaccines.