A monkeypox nanovaccine candidate based on three protein antigens and silica nanoparticles.

Monkeypox (Mpox), a zoonotic viral disease characterized by strong pathogenicity and transmissibility, necessitates the development of safe and effective vaccine. A protein-based vaccine holds great promise due to its high safety and strong specificity. A29L and M1R from intracellular mature virion and A35R from extracellular enveloped virion are immunodominant antigens capable of providing adequate antigen coverage. However, these proteins necessitate the adjuvant and the delivery system to optimize the immunogenicity. Here, STG-982 (a STING agonist) was conjugated with the antigens to function as the adjuvant, and silica nanoparticles were utilized as the delivery system. The antigens were conjugated with silica nanoparticles via DogTag-DogCatcher system to form a nanovaccine. The vaccine induced robust antigen-specific antibody, balanced Th1/Th2 cytokine profiles, and strong CD4+ and CD8+ T-cell response. It further stimulated durable memory B- and T-cell populations and enhanced splenocyte proliferation. Remarkably, triple immunization conferred 100 % protection against lethal ectromelia virus challenge in BALB/c mice, with no observed organ toxicity. These results demonstrate a safe, potent, and durable vaccine platform against mpox that is adaptable to other emerging pathogens.