As the world continues to face the evolving threat of infectious diseases, including emerging zoonoses like mpox (formerly monkeypox), scientists are racing to develop vaccines that are not only safe and effective but also capable of rapid deployment in outbreak scenarios. A recent peer-reviewed study published in eBioMedicine provides timely and encouraging evidence in this pursuit. Researchers from The University of Tokyo, led by Associate Professor Kouji Kobiyama and Professor Ken J. Ishii, have evaluated the safety and immunogenicity of LC16m8, a live attenuated vaccinia virus originally developed for smallpox, for its use in protecting against mpox.
Originally approved in Japan for monkeypox in 2022, LC16m8 had shown promise in non-human primate models. The new study offers the first comprehensive cross-species evaluation of the vaccine’s safety profile and immune response. The research encompasses genetically diverse mouse models, non-human primates, and human volunteers, adding significant weight to its translational potential.
Robust Immunogenicity in Mouse Models
Three genetically distinct mouse strains—BALB/c, C57BL/6J, and CAST/EiJ—were used to assess LC16m8’s immunogenic properties. The vaccine stimulated strong humoral immune responses, including germinal center B cells and follicular helper T cells, both critical to long-term protection.
CAST/EiJ mice, which are more susceptible to viral infections, showed significantly reduced lung viral loads, demonstrating vaccine-induced protection against mpox. The immunological breadth across genetically diverse models suggests that LC16m8 could be effective across varied human genetic backgrounds.
Safety and Efficacy in Non-Human Primates
In cynomolgus monkeys, the vaccine induced localized pox lesions, as expected from vaccinia-based inoculations, but did not result in systemic illness or adverse physiological changes, such as abnormal temperature shifts, weight loss, or hematological abnormalities.
This preclinical safety data is critical, especially for regulatory bodies considering emergency or fast-track use authorizations in high-risk regions.
Human Trial Participants Showed Strong Neutralizing Responses
Blood samples from healthy human volunteers vaccinated with LC16m8 demonstrated the presence of neutralizing antibodies against multiple mpox virus (MPXV) variants. No serious adverse events were reported during the follow-up period. These findings suggest that LC16m8 may provide broad cross-protection and is well-tolerated in humans.
Implications for Global Health and Pandemic Preparedness
The study’s results position LC16m8 as a viable candidate for rapid deployment in mpox-endemic areas, particularly in parts of Africa where the virus continues to pose a public health burden. As Dr. Kobiyama notes, the validated safety and efficacy profiles of LC16m8 could expedite regulatory approval and strategic stockpiling, supporting global outbreak response frameworks.
Importantly, this research also serves as a proof of concept for developing vaccines using a cross-species evaluation pipeline, which could be replicated for other emerging viral threats. It aligns with WHO and GAVI priorities on vaccine platform versatility and rapid pathogen response strategies.
Remaining Challenges and Future Directions
While these findings are promising, the authors caution that further research is needed, particularly in:
- Naïve and immunocompromised populations, where vaccine safety and efficacy can differ significantly.
- Optimization of dosing strategies and the potential for booster regimens.
- Exploring alternative delivery platforms or formulations for broader distribution (e.g., thermostable formats for low-resource settings).
The study underscores the urgent need for global collaboration in building robust vaccine development pipelines that are proactive rather than reactive.
“Our work can shape and guide the development of a permanent global surveillance and response system for new infectious diseases, creating more resilient societies that are better prepared for future pandemic threats,” said Dr. Kobiyama.
This research was funded by the Japan Agency for Medical Research and Development (AMED) through several programs, including initiatives focused on emerging and re-emerging infectious diseases, vaccine development, and life science and drug discovery. Additional support was provided by the Ministry of Education, Culture, Sports, Science and Technology in Japan, reflecting a coordinated national effort to advance research on infectious disease prevention and vaccine innovation.
SOURCE:
Kobiyama, K., Utsumi, D., Kaku, Y., et al. Immunological analysis of LC16m8 vaccine: preclinical and early clinical insights into mpox. eBioMedicine, May 2025