Potent neutralization of Marburg virus by a vaccine-elicited antibody

"Marburg virus (MARV) is a filovirus that causes a severe and often lethal hemorrhagic fever1,2. Despite the increasing frequency of MARV outbreaks, no vaccines or therapeutics are licensed for use in humans. Here, we designed mutations that improve the expression, thermostability, and immunogenicity of the prefusion MARV glycoprotein (GP) ectodomain trimer, which is the sole target of neutralizing antibodies and vaccines in development38."

"We discovered a fully human, pan-marburgvirus monoclonal antibody, MARV16, that broadly neutralizes all MARV isolates as well as Ravn virus and Dehong virus with 40 to 100-fold increased potency relative to previously described antibodies9. Moreover, MARV16 provides therapeutic protection in guinea pigs challenged with MARV. We determined a cryo-electron microscopy structure of MARV16-bound MARV GP showing that MARV16 recognizes a prefusion-specific epitope spanning GP1 and GP2, blocking receptor binding and preventing conformational changes required for viral entry."

Mutations were introduced to the prefusion MARV glycoprotein ectodomain trimer to improve expression, thermostability, and immunogenicity. The prefusion GP trimer is the sole target of neutralizing antibodies and vaccines in development. A fully human, pan-marburgvirus monoclonal antibody, MARV16, was identified that broadly neutralizes all MARV isolates as well as Ravn and Dehong viruses with 40- to 100-fold increased potency compared with previously described antibodies. MARV16 provided therapeutic protection in guinea pig challenge models. Cryo-electron microscopy of MARV16 bound to MARV GP revealed recognition of a prefusion-specific epitope spanning GP1 and GP2, blocking receptor binding and preventing conformational changes required for viral entry.

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