High-quality antibody tests for SARS-CoV-2 are critical to understanding how the virus spreads through the population, also supporting the development of effective vaccines and therapies. 

The world’s scientists are discovering more about COVID-19 every day, but it has long been clear that there is an urgent need for a test sensitive enough to detect the viral antibodies in people who have shown no symptoms. Such a ground-breaking development could identify thousands more people who have already had the virus.  

Supported by the NIHR Birmingham Biomedical Research Centre, and the Institute of Global Innovation, experts at the Universities of Birmingham and Southampton have worked with leading in vitro diagnostic (IVD) company The Binding Site to create just such a test. The Birmingham test has detected antibodies in people who only suffered a mild form of COVID-19 infection. These people may have displayed very few or no symptoms, but generated an immune response to the virus.

Professor Alex Richter, from the Institute of Immunology and Immunotherapy at Birmingham, commented: “It is relatively straightforward to detect antibodies in those who have experienced severe infections, but our research has shown that those who have had a milder or asymptomatic illness, usually have weaker antibodies responses, which means that cases could be being missed by the tests currently in use. 

“Our test detects antibodies created by the body’s reaction to SARS-CoV-2 spike protein. By using the correctly folded form of the spike protein in our assay, we are getting 98 per cent sensitivity in patients following mild disease. The test also works well with dry blood spot samples, which could signal a breakthrough for at-home sampling not just in the UK but potentially world-wide.” 

The breakthrough moment came when researchers found which antigen to include in the assay and how best to balance recognising IgG, IgA and IgM immunoglobulins. Further iterations are likely as the group’s understanding of the sustainability of the immune response deepens, including examining antibodies in saliva. 

The test was designed to detect all three immunoglobulins produced by the body to optimise the sensitivity and to increase detection at the earliest possible stage after exposure to the virus.

As well as working effectively for venous blood samples, the innovative test can also detect antibodies eluted from a dried blood spot. This opens up opportunities for a, home sampling solution, offering a more accurate testing capability in homes, businesses, airports as well as GP surgeries and hospitals round the world, including low and middle income countries.

The Birmingham approach to developing the test brings together the best of academia and industry. Working in partnership with The Binding Site provides researchers with access to the commercial organisation’s outstanding assay development teams. Working with The Binding Site also offers a ready route to commercialising the test – thanks to the partnership with a leading UK IVD company that has a direct presence in over 25 countries - producing a wide range of vital clinical tests, more than 90% of which are sold outside the UK. 

Adam Cunningham, Professor of Functional Immunity at Birmingham’s Institute of Immunology and Immunotherapy, commented: “Within 10 weeks, our partnership produced a world-leading antibody test that will soon be available to the NHS and will play a vital role in control of this pandemic and the evaluation of new vaccines.

“Our test is so sensitive because of the combination of high quality viral spike protein used in the test and our expertise in knowing how to maximize the quality of signal detected. Colleagues at Southampton University, led by Prof Max Crispin, had produced a native version of spike protein and we have used this in the test, as it is excellent for capturing the diverse antibodies present in the blood. This allows us to detect antibodies in more people at an earlier time point after infection.”

Professors Alex Richter and Adam Cunningham discuss the development of the test with The Binding Site.

The most important difference between this test and some of the tests recently promoted by the UK Government, is that existing tests use the nucleocapsid protein (NP) - a protein that binds nucleic acids within the virus but plays no role in host cell binding and entry.  

“Antibody testing may be vital to evaluate how long someone remains immune – particularly in calculating the longevity of immunity to the antigen targeted by neutralising antibodies,” added Professor Cunningham. “Seroprevalence studies to measure antibodies in the UK population will only have impact if they are sensitive enough to detect antibodies in all people infected by the virus.

“As the Oxford and Imperial College vaccines enter phase 2 and 3 trials, we must have an antibody test that identifies the correct form of protective immunity to this virus so that we can rationally compare which vaccine is most effective.”

The Birmingham test also provided evidence to confirm COVID-19 as the cause of a multi-system inflammatory syndrome in children who tested negative for the virus by the PCR test, which directly detects the presence of an antigen, rather than antibodies.

This raises the possibility that children who may have had the virus could be at risk of developing this new condition known as Paediatric Inflammatory Multi-System Syndrome - Temporally associated with SARS-CoV-2 (PIMS-TS). Emerging during the pandemic, PIMS-TS causes children to present with symptoms similar to those seen in Kawasaki disease - a rare condition usually seen in under-fives that causes persistently high temperature, rashes and inflammation of blood vessels.

Researchers worked with Birmingham Women’s and Children’s NHS Foundation Trust and found these children displayed high levels of anti-SARS-CoV-2 antibodies, the pattern of which indicated that the infection most likely occurred many weeks or even months previously.

“We’re hugely proud of our partnership which has used our highly sensitive antibody test to help identify children with PIMS-TS from other patients with similar symptoms,” said Professor Richter.

“The current pandemic represents a previously unimaginable global challenge. Without vaccination, the role of antibody testing, as a means to assess community asymptomatic spread of infection, is of paramount importance. The test will help to guide public health measures to control the spread of COVID-19 by accurately identifying the proportion of communities that are now immune.

"This partnership has drawn together unrivalled academic, clinical and commercial expertise in antibody testing - creating the potential to deliver a reliable test in our fight against COVID-19.”


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