Clade IIb Mpox Less Harmful in Infected Mice
November 24, 2025
A new study in Nature Communications has provided key insights into mpox pathogenesis, showing that clade IIb infections produce milder disease in mice than clade IIa, due to faster viral clearance and stronger immune responses. This mouse model mirrors human infection patterns, offering a valuable tool for developing antivirals and vaccines. The research underscores how viral clade differences shape disease outcomes and transmission dynamics. As mpox cases rise again in Africa, with clade Ib driving the latest emergency, the findings highlight an urgent need for continued investment in next-generation vaccines, improved surveillance, and research bridging laboratory discoveries to public health action.
A recent Nature Communications study has advanced scientific understanding of mpox by comparing disease outcomes between clade IIa and IIb in mouse models. Researchers at the University of Veterinary Medicine Hannover found that clade IIb infection—responsible for the 2022 global outbreak—induces stronger immune responses, faster viral clearance, and less severe clinical disease than clade IIa. This model, which replicates human transmission through intradermal infection, is the first to closely mirror both the epidemiology and symptoms seen in current human outbreaks.
The findings are timely, as the ongoing mpox upsurge in Central Africa, driven by clade Ib, continues to strain regional health systems. Clade I infections have shown mortality rates as high as 10%, compared to less than 4% in clade II infections. In conflict zones such as eastern Democratic Republic of the Congo, transmission has been exacerbated by displacement, limited vaccination coverage, and high-risk work environments, including mining regions.
Lead researcher Dr. Asisa Volz and her team demonstrated that clade IIb’s rapid immune activation could explain its lower disease severity in humans. The model provides an essential platform for evaluating antiviral drugs and vaccines, including potential mRNA-based approaches that may improve upon the smallpox-derived JYNNEOS vaccine currently used.
Experts such as Dr. Chris Beyrer of Duke University stress that the study illustrates both scientific progress and a global policy gap. While the virus continues to evolve, international preparedness and funding for mpox research remain insufficient.
This study reinforces that understanding clade-specific immune dynamics is critical for developing targeted countermeasures. With mpox retaining epidemic potential, the world cannot afford complacency. Translating animal model findings into effective vaccines and therapeutics must be a global priority to prevent the next widespread outbreak.