Antibodies to distinct epitopes on MPXV enveloped virion provide additive and complete protection.

A paired anti-A35 plus anti-B6 monoclonal antibody combination gives additive and complete protection against morbidity and mortality in a lethal VACV mouse model.

• Why it matters: Ongoing MPXV evolution and lack of effective poxvirus therapies create a need to define protective antibody targets on extracellular enveloped virions.
• What they did: Human monoclonal antibodies were isolated from an antibody library and mapped to distinct epitopes on EV A35 and B6 antigens, including four A35 groove binders and one A35 loop binder plus three B6 epitope binders.
• The result: Targeting EV epitopes on both A35 and B6 yields additive and complete protection in lethal VACV mice, suggesting full protection does not require simultaneous targeting of EV and MV forms.

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