LONDON – Oxford Immunotec plc is aiming to plug a significant gap in the COVID-19 diagnostics landscape, with the development of a commercial clinical grade test for quantifying T cell responses to the SARS-CoV-2 virus.

T-Spot Discovery SARS-CoV-2, currently available for research use only, is based on the same automated technology as the company’s tuberculosis diagnostic, which is approved for use in more than 60 countries. The SARS-CoV-2 test is now undergoing assessment as part of a 3,000-person study of diagnostics tests funded by the U.K. government agency Public Health England (PHE).

“The principle and the technology of the test are identical between tuberculosis and COVID,” said Peter Wrighton-Smith, CEO of Oxford Immunotec. “We are bringing standardized, clinically approved technology to market,” he told BioWorld.

As the pandemic progresses, the need to reliably measure SARS-CoV-2-specific T cell responses at scale is becoming more evident, both to address limitations of polymerase chain reaction (PCR) tests used to detect the virus and of serology tests for antibodies and to provide a bigger picture of the overall immune response.

A standardized method of measuring T cell responses would be useful in assessing and comparing the various COVID-19 vaccines that are in development, helping to define the correlates of protection that make for an effective immune response.

PCR tests for SARS-CoV-2 are highly specific and can detect the virus early in the course of infection, but they do not show if it is still replicating and cannot say if someone has been infected and recovered.

Antibody tests have the advantages that they are rapid, low cost and can detect past exposure. But they do not indicate if a person is contagious. If the antibody response is delayed or has waned, serology tests can give false negative results.

According to one study of patients who recovered from COVID-19, between 10% and 30% had no detectable antibody response.

Meanwhile, evidence is accumulating that T cell-mediated immune responses are generated in advance of antibody responses, T cells play an important role in recovery from the infection and T cell responses occur in people who do not generate SARS-CoV-2 antibodies.

Researchers at the Karolinska Institute in Stockholm detected T cell responses in people with no antibody response, suggesting antibody tests alone are leading to underestimates of the numbers who have been exposed to the virus, and that T cell responses might be a more sensitive indicator.

As one of only two companies in the world with a commercial T cell clinical diagnostic, Oxford Immunotec has been following emerging data on the role of T cell responses in COVID-19 infection and working to translate its proprietary tuberculosis technology to SARS-CoV-2. The research kit has been available since mid-May.

“Our conviction on what we can offer in this area is growing,” said Wrighton-Smith. “We have an affordable technology that can be done in high volumes [and] in a standardized way.”

One of the key advantages is that while most antibody tests give a yes/no answer, T Spot can look at the strength and breadth of the T cell-mediated immune response.

T Spot uses peripheral blood mononuclear cells, which are isolated from a routine blood sample before being washed to remove any confounding factors and decanted into well plates, with each plate holding 250,000 cells.

CD4 and CD8 T cells exposed to the virus are activated and develop into SARS-CoV-2-specific T cells. When stimulated in vitro with SARS-CoV-2 antigens, these activated cells produce interferon gamma, which is measured in the assay.

“This is an approved and standardized platform. You can run the test in Shanghai, Singapore, London and San Francisco,” said Wrighton-Smith.

The PHE study is using T Spot to assess immune responses (or not) in volunteer frontline workers in health care, the fire service and the police force.

It will assess a number of aspects, Wrighton-Smith said. “For example, there will be a subset of people who have had a positive PCR test. We want to figure out how many produce T cells and what the T cell response looks like.”

Because the samples also are being tested for antibodies, it will be possible to see if T Spot can pick up past infections missed by serology testing.

The value of having an alternative method of assessing if people have been infected is underlined by early data from the study. Of the one-third of the key workers who had experienced symptoms they believed were caused by COVID-19 – but who had not had a confirmatory PCR test – only half had detectable antibodies.

Wrighton-Smith said the T Spot test promises to be an important addition to serology testing in assessing immune responses to COVID-19 vaccines that are in development. Oxford-based Oxford Immunotec is in talks with manufacturers about using the test in trials of vaccines.

With the number of people who have been infected on the rise, T cell testing would be more precise than antibody tests in prescreening volunteers to ensure they have not had previous exposure to the virus and already have developed immunity.

In addition, there is data indicating previous infection with other coronaviruses, including the common cold, confers some level of protection against SARS-CoV-2, which again could confound vaccines trials.

The five panels of antigens used in the T Spot assay have been selected from the whole of the virus, but exclude any sequences with high homology to other coronaviruses, allowing the breadth of the immune response to be measured while minimizing cross reactivity. “You can tell if people have been exposed or not, specifically to SARS-CoV-2,” Wrighton-Smith said.