A cell-based, SARS-CoV-2 spike protein interaction assay to inform the neutralising capacity of recombinant and patient sera antibodies

Frontiers in Virology

Virology

Chiara Pallini¹  Omar S. Qureshi¹  Cristina Matas de las Heras¹  Ana Teodosio¹  Neale Harrison¹  Ines Morano¹  Zhi Li¹  Catherine A. Brady¹  Elizabeth Jinks¹  Jamie Cowley¹  Andrea S. Lavado¹  Ayesha Ashraf¹  Lauren Richardson¹  Hujo Chan¹  John Gordon¹  Robert Moring¹  Nicholas M. Barnes²  Aekkachai Tuekprakhon³  Zania Stamataki³  Harriet J. Hill³  Timothy R. Dafforn⁴  Lawrence S. Young⁵  Dimitris K. Grammatopoulos⁶ 

[1] Celentyx Ltd, Birmingham Research Park, Birmingham, United Kingdom;Celentyx Ltd, Birmingham Research Park, Birmingham, United Kingdom;Neuropharmacology Research Group, Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom;Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom;School of Biosciences, University of Birmingham, Birmingham, United Kingdom;Warwick Medical School and Global Research Priority in Health, University of Warwick, Coventry, United Kingdom;Warwick Medical School and Global Research Priority in Health, University of Warwick, Coventry, United Kingdom;Pathology and Institute of Precision Diagnostics and Translational Medicine, University Hospital Coventry and Warwickshire NHS Trust, Coventry, United Kingdom;

关键词: SARS-CoV-2;    ACE2;    spike protein;    antibody discovery;    virology;    variant;    antiviral;   

DOI  :  10.3389/fviro.2023.1163385

 received in 2023-02-10, accepted in 2023-06-21,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionThe engagement of the SARS-CoV-2 spike protein with ACE2 is a critical step for viral entry to human cells, and, therefore, blocking this interaction is a major determinant of the efficacy of monoclonal antibody therapeutics and vaccine elicited serum antibodies. The emergence of SARS-CoV-2 variants has necessitated the development of adaptable assays that can be applied to assess the effectiveness of antibody-based therapeutics.MethodsThrough the testing of a range of recombinant spike proteins, we have developed a cell-based, ACE2/spike protein interaction assay that characterises monoclonal anti-spike protein antibodies and neutralising antibodies in donor serum. The assay uses high-content imaging to quantify cell-bound spike protein fluorescence.ResultsUsing spike proteins from the original “Wuhan” SARS-CoV-2 strain and the Delta and Omicron variants, we identified differential blocking activity of three monoclonal antibodies directed against the spike receptor-binding domain. Importantly, biological activity in the spike interaction assay translated to efficacy in a SARS-CoV-2 infection assay.DiscussionThe spike protein interaction assay can be used to monitor anti-spike antibodies against the major known SARS-CoV-2 variants and is readily adaptable for quantification of the impact of antibodies against new and emerging SARS-CoV-2 variants.

【 授权许可】

Unknown   
Copyright © 2023 Harrison, Richardson, Pallini, Morano, Jinks, Cowley, Chan, Hill, Tuekprakhon, Li, Matas de las Heras, Teodosio, Lavado, Moring, Ashraf, Dafforn, Grammatopoulos, Gordon, Brady, Young, Barnes, Stamataki and Qureshi