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Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration.
Fiedler, Sebastian; Devenish, Sean R A; Morgunov, Alexey S; Ilsley, Alison; Ricci, Francesco; Emmenegger, Marc; Kosmoliaptsis, Vasilis; Theel, Elitza S; Mills, John R; Sholukh, Anton M; Aguzzi, Adriano; Iwasaki, Akiko; Lynn, Andrew K; Knowles, Tuomas P J.
  • Fiedler S; Fluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge, CB1 8DH, UK. sebastian.fiedler@fluidic.com.
  • Devenish SRA; Fluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge, CB1 8DH, UK.
  • Morgunov AS; Fluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge, CB1 8DH, UK.
  • Ilsley A; Yusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
  • Ricci F; Fluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge, CB1 8DH, UK.
  • Emmenegger M; Fluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge, CB1 8DH, UK.
  • Kosmoliaptsis V; Institute of Neuropathology, University of Zurich, 8091, Zurich, Switzerland.
  • Theel ES; Department of Surgery, University of Cambridge, Addenbrookes Hospital, Cambridge, CB2 0QQ, UK.
  • Mills JR; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, University of Cambridge, Hills Road, Cambridge, CB2 0QQ, UK.
  • Sholukh AM; NIHR Cambridge Biomedical Research Centre, Hills Road, Cambridge, CB2 0QQ, UK.
  • Aguzzi A; Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Iwasaki A; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Lynn AK; Center for MS and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA.
  • Knowles TPJ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Sci Rep ; 12(1): 19791, 2022 Nov 17.
Article in English | MEDLINE | ID: covidwho-2119245
ABSTRACT
The effectiveness of therapeutic monoclonal antibodies (mAbs) against variants of the SARS-CoV-2 virus is highly variable. As target recognition of mAbs relies on tight binding affinity, we assessed the affinities of five therapeutic mAbs to the receptor binding domain (RBD) of wild type (A), Delta (B.1.617.2), and Omicron BA.1 SARS-CoV-2 (B.1.1.529.1) spike using microfluidic diffusional sizing (MDS). Four therapeutic mAbs showed strongly reduced affinity to Omicron BA.1 RBD, whereas one (sotrovimab) was less impacted. These affinity reductions correlate with reduced antiviral activities suggesting that affinity could serve as a rapid indicator for activity before time-consuming virus neutralization assays are performed. We also compared the same mAbs to serological fingerprints (affinity and concentration) obtained by MDS of antibodies in sera of 65 convalescent individuals. The affinities of the therapeutic mAbs to wild type and Delta RBD were similar to the serum antibody response, indicating high antiviral activities. For Omicron BA.1 RBD, only sotrovimab retained affinities within the range of the serum antibody response, in agreement with high antiviral activity. These results suggest that serological fingerprints provide a route to evaluating affinity and antiviral activity of mAb drugs and could guide the development of new therapeutics.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / COVID-19 Drug Treatment Type of study: Experimental Studies Topics: Variants Limits: Humans Language: English Journal: Sci Rep Year: 2022 Document Type: Article Affiliation country: S41598-022-22214-z

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / COVID-19 Drug Treatment Type of study: Experimental Studies Topics: Variants Limits: Humans Language: English Journal: Sci Rep Year: 2022 Document Type: Article Affiliation country: S41598-022-22214-z