Multi-epitope antibody cocktails protect mice against mpox and vaccinia
- Human monoclonal antibodies were isolated from donors with prior vaccinia exposure, using mpox A35 as bait; they bind several distinct epitopes and cross-react across orthopoxviruses.
- Cryo-EM showed the high-affinity antibody HD15 binds a conserved site at the A35 dimer interface.
- Pairing antibodies against non-overlapping epitopes gave synergistic, Fc-dependent neutralization in vitro and therapeutic protection in mice after vaccinia or mpox challenge, supporting a single-antigen, multi-epitope approach.
💡 Points Based on the abstract
Fc-dependent synergy is the double-edged detail: it implies effector function, not just blocking, drives protection, so mouse Fc engagement may not mirror human FcγR biology. A single-antigen cocktail also needs escape-mutant data,. And the comparator that matters is the existing standard (tecovirimat, vaccinia immune globulin), plus dosing windows after lesion onset.
📄 Paper · Science Translational Medicine ↗ Human antibody combinations determined by epitope mapping of orthopoxvirus A33/A35 confer therapeutic protection in mice