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An affinity-enhanced, broadly neutralizing heavy chain-only antibody protects against SARS-CoV-2 infection in animal models.
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.
  • Schepens B; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • van Schie L; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Nerinckx W; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Roose K; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Van Breedam W; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Fijalkowska D; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Devos S; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Weyts W; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • De Cae S; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Vanmarcke S; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Lonigro C; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Eeckhaut H; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Van Herpe D; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Borloo J; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Oliveira AF; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Catani JPP; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Creytens S; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • De Vlieger D; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Michielsen G; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Marchan JCZ; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Moschonas GD; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Rossey I; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Sedeyn K; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Van Hecke A; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Zhang X; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Langendries L; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Jacobs S; VIB Discovery Sciences, Technologiepark-Zwijnaarde 104B, 9052 Ghent, Belgium.
  • Ter Horst S; VIB Discovery Sciences, Technologiepark-Zwijnaarde 104B, 9052 Ghent, Belgium.
  • Seldeslachts L; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Liesenborghs L; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Boudewijns R; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Thibaut HJ; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Dallmeier K; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Velde GV; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Weynand B; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Beer J; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Schnepf D; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Ohnemus A; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Remory I; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Foo CS; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Abdelnabi R; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Maes P; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Kaptein SJF; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Rocha-Pereira J; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Jochmans D; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Delang L; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
  • Peelman F; KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, 3000 Leuven, Belgium.
  • Staeheli P; GVN, Global Virus Network, Baltimore, MD 21201, USA.
  • Schwemmle M; KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, 3000 Leuven, Belgium.
  • Devoogdt N; GVN, Global Virus Network, Baltimore, MD 21201, USA.
Sci Transl Med ; 13(621): eabi7826, 2021 Nov 24.
Article in English | MEDLINE | ID: covidwho-1450584
ABSTRACT
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 Sarbecovirus outbreaks. Camelid-derived single domain antibodies (VHHs) exhibit potent antimicrobial activity and are being developed as SARS-CoV-2­neutralizing 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 anti­COVID-19 biologic that is now being evaluated in the clinic.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / COVID-19 Type of study: Experimental Studies Topics: Variants Limits: Animals / Humans Language: English Journal: Sci Transl Med Journal subject: Science / Medicine Year: 2021 Document Type: Article Affiliation country: Scitranslmed.abi7826

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / COVID-19 Type of study: Experimental Studies Topics: Variants Limits: Animals / Humans Language: English Journal: Sci Transl Med Journal subject: Science / Medicine Year: 2021 Document Type: Article Affiliation country: Scitranslmed.abi7826