Detection and quantification of antibody to SARS CoV 2 receptor binding domain provides enhanced sensitivity, specificity and utilityMore about Open Access at the Crick
Authors listCarolina Rosadas Maryam Khan Eleanor Parker Federica Marchesin Ksenia Katsanovskaja Macià Sureda-Vives Natalia Fernandez Paul Randell Ruth Harvey Alice Lilley Benjamin HL Harris Mohamed Zuhair Michael Fertleman Samreen Ijaz Steve Dicks Charlotte-Eve Short Rachael Quinlan Graham P Taylor Kai Hu Paul McKay Annachiara Rosa Chloe Roustan Mark Zuckerman Kate El Bouzidi Graham Cooke Barnaby Flower Maya Moshe Paul Elliott Alexandra J Spencer Teresa Lambe Sarah C Gilbert Hugh Kingston J Kenneth Baillie Peter JM Openshaw Malcolm G Semple Peter Cherepanov Myra O McClure Richard S Tedder ISARIC4C Investigators
Toggle all authors (39)
Accurate and sensitive detection of antibody to SARS-CoV-2 remains an essential component of the pandemic response. Measuring antibody that predicts neutralising activity and the vaccine response is an absolute requirement for laboratory-based confirmatory and reference activity. The viral receptor binding domain (RBD) constitutes the prime target antigen for neutralising antibody. A double antigen binding assay (DABA), providing the most sensitive format has been exploited in a novel hybrid manner employing a solid-phase S1 preferentially presenting RBD, coupled with a labelled RBD conjugate, used in a two-step sequential assay for detection and measurement of antibody to RBD (anti-RBD). This class and species neutral assay showed a specificity of 100% on 825 pre COVID-19 samples and a potential sensitivity of 99.6% on 276 recovery samples, predicting quantitatively the presence of neutralising antibody determined by pseudo-type neutralisation and by plaque reduction. Anti-RBD is also measurable in ferrets immunised with ChadOx1 nCoV-19 vaccine and in humans immunised with both AstraZeneca and Pfizer vaccines. This assay detects anti-RBD at presentation with illness, demonstrates its elevation with disease severity, its sequel to asymptomatic infection and its persistence after the loss of antibody to the nucleoprotein (anti-NP). It also provides serological confirmation of prior infection and offers a secure measure for seroprevalence and studies of vaccine immunisation in human and animal populations. The hybrid DABA also displays the attributes necessary for the detection and quantification of anti-RBD to be used in clinical practice. An absence of detectable anti-RBD by this assay predicates the need for passive immune prophylaxis in at-risk patients.
Journal Journal of Virological Methods