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Article Dans Une Revue Science Translational Medicine Année : 2023

Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody

Emma Esterman
Janne Tynell
Remigius Gröning
Yan Sun
Anna Wec
Markus Keller
Clas Ahlm
C. Garrett Rappazzo
Rainer Ulrich
Larry Zeitlin
James Geoghegan
  • Fonction : Auteur
Mattias N.E. Forsell
Laura Walker
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Résumé

Emerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus-experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb: It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb's accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic.
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Dates et versions

pasteur-04129288 , version 1 (15-06-2023)

Identifiants

Citer

Eva Mittler, Alexandra Serris, Emma Esterman, Catalina Florez, Laura Polanco, et al.. Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody. Science Translational Medicine, 2023, 15 (700), pp.eadg1855. ⟨10.1126/scitranslmed.adg1855⟩. ⟨pasteur-04129288⟩
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