Author:
Harrison Neale,Richardson Lauren,Pallini Chiara,Morano Ines,Jinks Elizabeth,Cowley Jamie,Chan Hujo,Hill Harriet J.,Tuekprakhon Aekkachai,Li Zhi,Matas de las Heras Cristina,Teodosio Ana,Lavado Andrea S.,Moring Robert,Ashraf Ayesha,Dafforn Timothy R.,Grammatopoulos Dimitris K.,Gordon John,Brady Catherine A.,Young Lawrence S.,Barnes Nicholas M.,Stamataki Zania,Qureshi Omar S.
Abstract
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.