The global re-emergence of monkeypox virus (MPXV) has created a critical need for effective and well-tolerated vaccines to prevent infection, limit disease severity, and reduce transmission. As an orthopoxvirus related to smallpox, mpox presents a unique public health challenge, especially for immunocompromised populations.
Current prevention strategies rely on repurposed smallpox vaccines, including ACAM2000 and JYNNEOS. While these vaccines provide some cross-protection, they were not designed specifically for mpox and come with notable safety concerns. ACAM2000, a live virus vaccine, poses risks of severe side effects, while JYNNEOS, though safer, still lacks optimal efficacy for mpox-specific immunity. There remains a clear need for a safer and more targeted vaccine solution.
This vaccine candidate targets the globular N-terminal domain (residues 1–366) of the monkeypox virus antigen OPG153. The antigen is expressed in FreeStyle 293-F cells, purified, and validated for high-affinity binding to broadly neutralizing antibodies. Immunization studies in BALB/c mice showed robust neutralizing responses against MPXV-IIb and vaccinia virus when the antigen was formulated with AddaVax adjuvant. The vaccine also demonstrated cross-reactivity with other orthopoxvirus OPG153 orthologs.
Nucleic acid constructs encoding engineered OPG153 variants are optimized for enhanced expression and stability and can be delivered via lipid nanoparticles or adjuvants to promote protective immune responses and reduce viral shedding. This approach is distinct in its use of a novel viral antigen, identified through structure-guided design, and demonstrates improved immunogenicity compared to existing vaccines.
Provisional US patent filed 05/09/2025