Details

Autor(en) / Beteiligte

• Schepens, Bert
• van Schie, Loes
• Nerinckx, Wim
• Roose, Kenny
• Van Breedam, Wander
• Fijalkowska, Daria
• Devos, Simon
• Weyts, Wannes
• De Cae, Sieglinde
• Vanmarcke, Sandrine
• Lonigro, Chiara
• Eeckhaut, Hannah
• Van Herpe, Dries
• Borloo, Jimmy
• Oliveira, Ana Filipa
• Catani, João Paulo Portela
• Creytens, Sarah
• De Vlieger, Dorien
• Michielsen, Gitte
• Marchan, Jackeline Cecilia Zavala
• Moschonas, George D
• Rossey, Iebe
• Sedeyn, Koen
• Van Hecke, Annelies
• Zhang, Xin
• Langendries, Lana
• Jacobs, Sofie
• Ter Horst, Sebastiaan
• Seldeslachts, Laura
• Liesenborghs, Laurens
• Boudewijns, Robbert
• Thibaut, Hendrik Jan
• Dallmeier, Kai
• Velde, Greetje Vande
• Weynand, Birgit
• Beer, Julius
• Schnepf, Daniel
• Ohnemus, Annette
• Remory, Isabel
• Foo, Caroline S
• Abdelnabi, Rana
• Maes, Piet
• Kaptein, Suzanne J F
• Rocha-Pereira, Joana
• Jochmans, Dirk
• Delang, Leen
• Peelman, Frank
• Staeheli, Peter
• Schwemmle, Martin
• Devoogdt, Nick
• Tersago, Dominique
• Germani, Massimiliano
• Heads, James
• Henry, Alistair
• Popplewell, Andrew
• Ellis, Mark
• Brady, Kevin
• Turner, Alison
• Dombrecht, Bruno
• Stortelers, Catelijne
• Neyts, Johan
• Callewaert, Nico
• Saelens, Xavier

Titel

An affinity-enhanced, broadly neutralizing heavy chain-only antibody protects against SARS-CoV-2 infection in animal models

Ist Teil von

• Science translational medicine, 2021-11, Vol.13 (621), p.eabi7826

Ort / Verlag

United States

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Broadly neutralizing antibodies are an important treatment for individuals with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Antibody-based therapeutics are also essential for pandemic preparedness against future outbreaks. Camelid-derived single domain antibodies (VHHs) exhibit potent antimicrobial activity and are being developed as SARS-CoV-2–neutralizing antibody-like therapeutics. Here, we identified VHHs that neutralize both SARS-CoV-1 and SARS-CoV-2, including now circulating variants. We observed that the VHHs bound to a highly conserved epitope in the receptor binding domain of the viral spike protein that is difficult to access for human antibodies. Structure-guided molecular modeling, combined with rapid yeast-based prototyping, resulted in an affinity enhanced VHH-human immunoglobulin G1 Fc fusion molecule with subnanomolar neutralizing activity. This VHH-Fc fusion protein, produced in and purified from cultured Chinese hamster ovary cells, controlled SARS-CoV-2 replication in prophylactic and therapeutic settings in mice expressing human angiotensin converting enzyme 2 and in hamsters infected with SARS-CoV-2. These data led to affinity-enhanced selection of the VHH, XVR011, a stable anti–COVID-19 biologic that is now being evaluated in the clinic.