nCoV: Serological detection of past SARS-CoV-2 infection by non-invasive sampling for field epidemiology and quantitative antibody detection

Lead Research Organisation: Imperial College London


The principal method protecting susceptible populations from the importation of the novel Chinese coronavirus is to quarantine individuals at risk of the infection when they enter the country. If a person has symptoms of a chest infection it may be possible to diagnose or exclude coronavirus by a specific test for the virus. The limitation is that some people may have no symptoms and not be tested and indeed some may have been infected and recovered from the virus by the time of this testing. At present we have no specific serological method of detecting past infection with SARS-CoV-2 which may be important in defining unexpected infection risks. In practice this crucial lack can mean that ongoing transmission of virus infection may remain undetected. This programme of work will develop diagnostic tests a way in which samples can easily be taken by sampling fluid from the mouth and tested for antibody. An additional advantage is that this can allow screening of potential donors recovered from infection whose blood contain high levels of antibody which may be appropriate for treating patients with severe disease at a time that there are no recognised effective antiviral agents for patients.

Technical Summary

This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project.

The escalating numbers of affected individuals in China and the potential for importation of this infection to the UK during the pre-symptomatic and potentially infectious stage renders containment problematic. Acute diagnostic PCR is of short duration usefulness in identifying those recovered from the infection. The pattern of disease is clinically diffuse rendering identification of previous infections through clinical history very difficult. Here we describe the commitment of an exceptional and highly capable scientific group who, including the PI, have previously developed specific, sensitive serology for Ebola, Zika and Lassa. The Ebola tests were instrumental in the identification of seropositive persons who had recovered silently from Ebola and characterising their antibody response. Following the same methodology for SARS-CoV-2 will allow specific detection of antibody rather than placing reliance on SARS serological assays, permitting measurement of the penetration of this infection into any susceptible population. A test format will also be developed for the non-invasive sampling of oral fluid for G and M class antibody. Recombinant envelope proteins S1 and S2 and nucleoprotein will allow the sensitive detection of antibody. Our assays, also adaptable for Point of Care and diagnostic use, will be rendered specific by described methods for conjugate quenching previously developed by the group for Zika(1). Having serology which is diagnostically important for public health, herd immunity measures will also enable establishing WHO international standards. Measurement of neutralising antibody will be important for vaccine studies and characterisation of convalescent plasma(2).


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Description The present invention is directed to a method for detecting the presence or absence of SARS-Cov-2 antibodies in a sample, the method comprising: a. contacting the sample with a solid-phase support having a fusion protein immobilised thereto, said fusion protein comprising a first antigen and a scaffold polypeptide, 1. wherein the first antigen is a SARS-Cov-2 receptor binding domain polypeptide that binds anti-SARS-Cov-2 antibody, and ii. wherein the scaffold polypeptide immobilises the fusion protein to the solid-phase support and presents the first antigen away from the solid-phase support; b. allowing SARS-Cov-2 antibodies present in the sample to bind to the first antigen, thereby forming a complex of first antigen and SARS-Cov-2 antibody; c. contacting said complex with a labelled second antigen, wherein said labelled second antigen comprises a SARS-Cov-2 receptor binding domain polypeptide that binds SARS-Cov-2 antibody; d. allowing said labelled second antigen to bind to SARS-Cov-2 antibody present in the sample; e. removing labelled second antigen that is not bound to said complex; and f. detecting the presence of labelled second antigen bound to said complex; wherein the presence of labelled complex indicates the presence of SARS-Cov-2 antibody in the sample, and wherein the absence of labelled complex indicates the absence of SARS-Cov-2 antibody in the sample. 
IP Reference WO2022013574 
Protection Patent application published
Year Protection Granted 2022
Licensed No
Impact highest specificity and sensitivity, also predicts and measures neutralising antibody