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Nina Garrett, R&D director at Abingdon Health discusses the key role antibody testing is playing in the pandemic and how an integrated approach with vaccines could help normal life resume.
Millions of tests for COVID-19 are taken worldwide every day, as they become an increasingly important tool for our return to normality. Testing programmes have been rolled out by governments globally with the important purpose of tracking the spread of the SARS-CoV-2 virus and letting individuals know whether they are infectious or have antibodies against the virus, so that they can keep themselves and others safe. The three most common types of testing, PCR testing, antigen testing and antibody testing, have quickly become common terms in everyone’s vocabulary.
Although these three tests typically fall under the general category of ‘testing’, have very different functions and uses. PCR tests screen for the presence of viral RNA from a swab, detecting whether an individual is currently infected. However, these tests are expensive, and it can take 24 hours or longer to get a result. Antigen lateral flow tests, the type which use a small disposable cartridge, are similar to PCR in that they test for an active infection and can provide results in 15-30 minutes.
While these types of tests are important, they don’t tell the whole story, as they can’t provide information on whether an individual has built an immune response to COVID-19, either through vaccination or through a previous infection. This is where antibody tests come in. One type of antibody test in particular, which looks for a specific type of antibody, IgG antibodies to the virus’ spike protein, which includes antibodies that neutralise the virus, could be a powerful tool in supporting the path out of lockdown and beyond.
Following infection, the body produces antibodies targeting specific parts of the SARS-CoV-2 (COVID-19) virus, with both the virus’ Nucleocapsid protein and Spike protein being important in the context of antibody tests. The nucleocapsid protein is a multi-functional protein that exists inside the virus, and the spike protein is on the outside and is integral in penetrating human cells and initiating infection. Antibodies to the spike protein are termed ‘neutralising antibodies’, as they target the spike protein of SARS-CoV-2 and ‘neutralise’ the virus by interfering with its ability to enter human cells.
Immunologically, antibodies to the nucleocapsid protein are very important, but in the context of a pandemic, neutralising antibodies to the spike protein are key. A recent study published in Nature from David Khoury at the University of New South Wales showed that neutralising antibodies are highly predictive of immune protection.1 Like the antigen tests, these neutralising antibody tests operate on a lateral flow test device, that can detect SARS-CoV-2 antibodies from a small finger prick of blood in around 20 minutes.
“Antibody tests can also be used in conjunction to vaccines to better understand the duration of immunity, and to potentially prioritise individuals who haven’t built an immune response to the virus in vaccination roll-outs.”
The importance of antibody certificates
Because antibody tests detect neutralising antibodies rather than monitoring for an active infection, a positive result can prove that the immune system has developed the capacity to defeat a future infection. Antibody tests can therefore be used for a variety of purposes, including detecting a prior case of COVID-19, confirming whether or not someone has produced an immune response following infection, and to monitor the duration of antibody response to a vaccine.
Large-scale antibody testing can help identify individuals with an immune response, potentially helping governments reduce the level of restrictions they are subject to, and enabling them to return to the workplace, to take part in events and to socialise. This would be more secure than limiting access based on vaccination, since not everyone who receives a vaccine for COVID-19 produces a strong immune response. No vaccine has a 100% efficacy rate- antibody tests could be used alongside vaccinations to monitor the presence and duration of the immune response produced.
Antibody tests can also be used in conjunction to vaccines to better understand the duration of immunity, and to potentially prioritise individuals who haven’t built an immune response to the virus in vaccination roll-outs. For example, those with prior infection show a strong immune response after a single vaccination, with a recent review of studies showing that the first vaccine dose acts as a ‘boost’ for an immune response acquired after natural infection. Determining this response could help extend the supply of vaccines in areas of low availability by revealing the individuals who require only one shot, rather than two. Monitoring antibody response in the months and years following vaccination and infection can provide data to help guide a pathway out of lockdowns.
A new approach to COVID-19 testing
One way of implementing the benefits of these tests is to pair them with a smartphone app which scans the test and produces an ‘antibody certificate’ that can then act as a pass for travel and events. This could significantly reduce the number of tests that people are required to take. Our current approach to testing is focused on volume, as we encourage individuals to take as many antigen and PCR tests as possible to determine their infection status. This can be costly and time consuming, particularly for industries such as air travel. A single antibody test, however, could potentially provide a proof of immune response in the form of a certificate that could alleviate the need to test multiple times. For employers who are demanding regular or everyday antigen testing using a swab, an antibody certificate would be an easier and more convenient solution for bringing people back to the workplace.
Neutralising antibody tests can form one part of an integrated approach to testing which includes antigen and PCR tests. For instance if an individual is tested and no antibodies are detected it might still be necessary for them to take an antigen or PCR test if they want to board a plane. However, integrating antibody testing within the current strategy is necessary, as these tests provide insights that the others can’t, while helping to reduce the volume and cost of testing.
About the Author: Nina Garrett
Khoury, D.S., Cromer, D., Reynaldi, A. et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med (2021). https://doi.org/10.1038/s41591-021-01377-8