Abstract
The recent emergence and global spread of the human Monkeypox virus (MPXV), including its transmission to non-endemic regions, have raised significant global health concerns. In this proof-of-concept study, we developed a recombinant protein-based MPXV vaccine candidate, employing an innovative and versatile multivalent, self-assembled nanocage protein scaffold. Two immunogenic antigens derived from the contemporary circulating MPXV strain have been incorporated into a self-assembled non-structural protein-10 (NSP-10) scaffold, expressed, and purified using an Escherichia coli expression system without a purification tag. The vaccine candidate elicited strong antibody responses in mice and conferred protection against the lethal Vaccinia virus in an intranasal and skin pock in vivo study. Additionally, an intranasal challenge with the MPXV strain clade IIb in immunized mice demonstrated promising outcomes, including a significant reduction in viral titres and eliciting a robust neutralizing antibody response. This study demonstrates a feasible, scalable, and cost-effective approach for the development of the MPXV vaccine.