Antibody-mediated immunity has been a huge focus in the battle against Covid-19. But antibodies are transitory, with levels in the blood waning after a few months, and vaccine developers in particular are beginning to focus on the longer-lasting cellular immune response. Now one group is collaborating with Public Health England to validate a test for T cells primed against various parts of the virus.
“Our aim is to both identify the numbers of T cells and also what they’re reacting to, and to use that both for diagnosing the disease and to better understand immunity,” says Peter Wrighton-Smith, chief executive of Oxford Immunotec. The first step is participation in the UK government’s EDSAB-Home study – in which the group’s test holds a somewhat unique position.
The T-Spot Discovery Sars-CoV-2 test is the only T cell test in the trial – according to the protocol all the others are antibody test kits, from manufacturers including Abingdon Health, Omega Diagnostics, BBI Solutions and Ciga Healthcare. All the tests, including Oxford Immunotec’s, are to be evaluated in the home setting.
Public Health England has multiple aims with the trial, which could enable a mass testing programme to identify people who have had Covid-19. The initial purpose is to determine the various tests’ accuracy and how well they perform at the population level when read by patients as well as by healthcare professionals. But it is also intended to quantify coronavirus-responsive T cells in patients’ blood, and determine whether a T cell response correlates with antibody levels.
“Do some people produce antibodies but not T cells, or some people produce T cells but not antibodies?” asks Mr Wrighton-Smith. “If T cells are independent from antibodies, adding them into our diagnostic mix would increase our ability to detect patients.”
There is also an opportunity to better understand the breadth of the T cell response against the virus. There is some suggestion, Mr Wrighton-Smith says, that some parts of Sars-CoV-2 are shared with other endemic coronaviruses, and people who have pre-existing immunity to those could have greater protection against Sars-CoV-2.
Oxford Immunotec’s test can separately detect T cells primed against the virus’s spike and nucleocapsid proteins as well as some other viral antigens; comparing these levels with patients’ symptoms and survival could eventually help predict an individual’s risk of contracting Covid-19.
Data from the trial will emerge in “weeks, not months”, Mr Wrighton-Smith says.
Separately from Public Health England’s objectives, Oxford Immunotec has its own plans. It intends to seek CE marking and FDA approval for its test for pinpointing people who have had Covid-19, and data from EDSAB-Home will go towards regulatory submissions.
There are question marks: Mr Wrighton-Smith says it is too early to say when submissions or approvals might come. It is also not clear whether the T cell test will be eligible for the FDA’s emergency use authorisation programme. So far EUAs have only been used for viral RNA, antigen and antibody tests, with no cellular assay for Covid-19 having had any sort of regulatory endorsement.
“That doesn’t mean that the FDA might not be amenable to an accelerated process, particularly if the risk-benefit to the population justifies it, and we believe we’ll be able to show evidence that it does. But formally no mechanism exists,” he says.
T-Spot Discovery might be able to detect Covid-19 infection before antibody tests, as well as after antibody levels wane. There could be a period relatively early on where viral RNA is no longer detectable, but the patient is still symptomatic and antibodies have not yet been produced.
“T cells precede the antibody response because you need T cells to generate antibodies. There’s a potential indication for use there, in acute testing,” Mr Wrighton-Smith says.
And if a person does have a meaningful T cell response to Covid-19, this might be a better basis for the notion of an immunity passport than a relatively ephemeral antibody response.
Lastly there is a use case for Oxford Immunotec’s test in vaccine research. Those vaccines that elicit both a T cell and an antibody response might be more effective than those that provide one or the other, and it will be necessary to test patients’ levels to determine this. The test could also give insight into the longevity of responses, helping vaccine developers establish when to deliver a booster shot.
The possibilities are dizzying, but as with antibody tests this approach butts up against an unfortunate fact: there is, as yet, no definitive proof that an immune response, even a T cell-mediated one, actually provides protection against reinfection. Only when evidence for such a link mounts up sufficiently will Oxford Immunotec be able to achieve many of its longer-term aims.