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Publication Detail
Detection and quantification of antibody to SARS CoV 2 receptor binding domain provides enhanced sensitivity, specificity and utility
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Rosadas C, Khan M, Parker E, Marchesin F, Katsanovskaja K, Sureda-Vives M, Fernandez N, Randell P, Harvey R, Lilley A, Harris BHL, Zuhair M, Fertleman M, Ijaz S, Dicks S, Short CE, Quinlan R, Taylor GP, Hu K, McKay P, Rosa A, Roustan C, Zuckerman M, El Bouzidi K, Cooke G, Flower B, Moshe M, Elliott P, Spencer AJ, Lambe T, Gilbert SC, Kingston H, Baillie JK, Openshaw PJM, Semple MG, Cherepanov P, McClure MO, Tedder RS
  • Publication date:
    01/04/2022
  • Journal:
    Journal of Virological Methods
  • Volume:
    302
  • Status:
    Published
  • Print ISSN:
    0166-0934
Abstract
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 neutralization 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.
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