Potent neutralisation of Marburg virus by a vaccine-elicited antibody
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Article Date: 12 November 2025
Article URL: https://www.nature.com/articles/s41586-025-09868-1
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Summary
Researchers stabilised the prefusion Marburg virus (MARV) glycoprotein (GP) trimer to improve expression, thermostability and immunogenicity, then used it to identify a fully human monoclonal antibody, MARV16. MARV16 potently and broadly neutralises all tested MARV isolates as well as Ravn and Dehong viruses, showing 40–100-fold greater potency than previously described antibodies. The antibody provided therapeutic protection in guinea pigs. Cryo-electron microscopy reveals MARV16 recognises a prefusion-specific epitope across GP1 and GP2, blocking receptor binding and the conformational changes required for viral entry. The study also maps the MARV GP glycan cap that shields the receptor binding site and demonstrates that MARV16 can be combined with other receptor-binding-site (RBS) antibodies to form cocktail therapies that are hard for the virus to escape.
Key Points
- Stabilising mutations to the prefusion MARV GP trimer improved expression, thermostability and immunogenicity — creating a better vaccine antigen candidate.
- The team discovered MARV16, a fully human, pan-marburgvirus monoclonal antibody with broad neutralisation across MARV strains and related viruses (Ravn, Dehong).
- MARV16 is 40–100× more potent than previously reported MARV antibodies and provided therapeutic protection in a guinea-pig challenge model.
- Cryo-EM structure shows MARV16 binds a prefusion-specific epitope spanning GP1 and GP2, blocking receptor binding and preventing entry-related conformational changes.
- The study defines the MARV GP glycan cap architecture that shields the receptor binding site, revealing structural parallels with other filovirus GPs.
- MARV16 can co-bind with other RBS-directed antibodies; antibody cocktails require multiple viral mutations for escape, suggesting resilient therapeutic combinations.
- Overall, GP stabilisation plus MARV16 advance both vaccine antigen design and antibody-based therapeutics for Marburg virus preparedness.
Context and Relevance
Marburg virus causes severe haemorrhagic fever and outbreaks have become more frequent, yet there are no licensed human vaccines or therapeutics. This work addresses two urgent needs: a stabilised, better-expressed vaccine antigen and a highly potent broadly neutralising monoclonal antibody. The structural insights into the GP, glycan cap and antibody binding sites inform rational vaccine design and the development of antibody cocktails that could be more robust against viral evolution. These findings are directly relevant to outbreak preparedness, diagnostic design, and therapeutic strategy for filoviruses.
Why should I read this?
Short version: these authors found a vaccine-elicited antibody that smashes Marburg across strains and protects animals — and they show how it works at near-atomic detail. If you follow infectious disease, vaccine design or outbreak response, this paper saves you time by putting a lead antibody and a stabilised GP antigen on your radar for rapid development and combination therapies.