Sir John Bell: Antibody testing still a key element in the fight against coronavirus

In late March, Boris Johnson hailed antibody tests as a potential “game changer” in the fight against coronavirus. The concept seemed simple – a pregnancy-style test taken at home that would show within ten minutes if a person had ever caught Covid-19.

If the result was positive, that person would have the “green light” to return to work because their immune system would be ready to fight off the disease, the Prime Minister announced.

It was hoped the technology would be available within days. Yet, nearly four months later, the nation is still waiting for those “game changing” tests to arrive.

Sir John Bell, Regius Chair of Medicine at Oxford University for nearly two decades, and one of the country’s leading immunologists, is the man leading the government’s ongoing search for a reliable antibody test.

In his first major newspaper interview since taking on the job, Sir John accepted the public had been left “scratching heads” in recent months over the technology, while leading experts have questioned its usefulness.

“We’re making a lot of progress. But there’s been a lot of confusion over all this,” Sir John told the Daily Telegraph. “We need to cut through and tell people exactly what’s going on.”

Three major studies are currently ongoing to try and prove that Covid-19 antibodies confer immunity, but none have yet delivered their final results.

Scientists need to demonstrate not only that antibodies protect against further infection, but also how long the responses might last, Sir John said. Recent data has suggested the antibodies may disappear relatively quickly, possibly even after just a few months.

The T-cell problem

Moreover, in recent weeks Sir John’s team has been grappling with a new challenge that in a worst case scenario could mean ten-minute finger prick tests would simply “never happen”.

A growing body of evidence now suggests that antibodies may form only a fraction of the body’s defence against the virus, Sir John explained. Instead, a separate part of the immune system, a type of white blood cell called T-cells, may be largely responsible.

“Let me tell you what the problem is,” Sir John said. “Around half of the immune response to this virus is through antibodies, and the other half is cellular.

“The cellular response is the bit of this formula that we don’t have yet. We’re busy working on that.

“Ideally, you’d want a finger prick test that people could use at home for antibodies, and a similar test for T-cells. The trouble is that measuring T-cell response is complicated. You really have to do it in a lab.

“The idea of sitting at home and testing your T-cell response just won’t happen. It’s about the complexity.”

Earlier this week a widely reported study found that around 30 per cent of Swedish blood donors had developed T-cell immunity to coronavirus – twice the number of cases in which antibodies were detected.

Yet, Sir John still believes that antibody testing will have an important role to play. He pointed to previous outbreaks of SARS and MERS, other types of coronavirus, where scientists found T-cell responses were largely simultaneous with antibodies.

In other words, if a person had developed antibodies to SARS or MERS, they usually had the T-cell response too, and vice versa. The T-cell responses tended to last longer, adding hope that protection may be long lived.

“We’re hoping that Covid behaves in a similar way,” Sir John said.

“I wouldn’t worry too much about the Swedish study, it was quite small. If everybody who has an antibody response also has a strong cellular response, then it’s possible that antibody tests might tell you that people will be protected for a long period of time. That would be an extremely useful piece of information, but we just don’t know yet.”

Natural immunity

As the virus gradually fades after initially spreading quickly, UK scientists are now considering a so-called ‘challenge study’ where volunteers known to have Covid-19 antibodies and T-cells are deliberately reinfected to test their response, Sir John revealed.

“You can’t do that until you’ve got a salvage therapy, because the risk is that somebody gets sick,” he said.

“But I think some of the new neutralising therapies look pretty good so if somebody ever got sick, you could fix it. I suspect the challenge study will be in the mid-autumn or by the end of the year. That would be my bet.”

Sir John believes a large proportion of people may be naturally immune to Covid-19 through their T-cells, even if they have never been infected, because the cells can be primed by other coronaviruses, such as the common cold.

“There’s a lot of data that shows that we do have a cross reactivity of T-cells to coronaviruses,” he said.

“Whenever you get a head cold, there’s about a 50 per cent chance it’s a coronavirus, and all you get is a head cold and feel awful for four days. It goes away, but it may have left you protected against Covid, to some degree.”

Older danger

He added that a major new government study into T-cells may solve one of the key puzzles of Covid-19: why older people die from coronavirus in such large numbers.

“I’ve been struggling since the beginning to understand why only old people die of this disease,” he said.

“If you look at the statistics, if you're 25 years old, you’re almost never going to die of this. But, if you’re over 65, you've got a problem, and if you’re over 75 then you’ve got a big problem.

“We do know that people’s T-cell immunity declines after the age of 65 quite dramatically in a process called T-cell senescence.

“We also know, for example, that the flu vaccine doesn’t work very well in people over 70. As a result, they actually have to use a particularly souped-up vaccine for people over 70.

“So that would be a good explanation of why the elderly are so at risk from this disease.”

To test the theory, Sir John revealed that Public Health England has launched a major study codenamed ‘Vivaldi’ to test levels of T-cell response in thousands of care home residents across the country.

“We may be able to see detectable evidence of the lack of T-cell immunity to coronaviruses in that population,” he said.

“The T-cell samples came in over the weekend. They’re being tested right now, literally. I think it’s crucial.”

Antibody anticlimax

Meanwhile, the hunt for an accurate antibody test continues, although Sir John admitted it got off to a rocky start. Days after the Prime Minister’s infamous “game changer” announcement in March, Sir John and his team at Oxford University discovered the 3.5 million antibody tests ordered by the government from China were effectively useless.

“Those first ones turned out to be pretty lousy,” he said. “They were never going to be game changers, I’m afraid.”

In May, finger prick tests produced in private labs and sold in Superdrug and Boots were abruptly banned by the Medicines & Healthcare products Regulatory Agency (MHRA) watchdog, partly over concern that the tests were inaccurate, but also over fears that people might take false hope from a positive result.

“I think it’s fair to say that people got a bit excited about some of these technologies before they were really ready for prime time,” Sir John said.

“They were pushed out there very quickly. Then I think the leadership realised that, actually, we’re not entirely sure what it means in terms of letting people roam around, or giving them the famous immunity passport. Does it mean you can go to work and not be worried about it? And the answer to all those questions is – we don’t know.

“And so they have rather wisely stepped back and said let’s do the studies to work out what we’re doing.”

Personal attacks

Some private suppliers even launched personal attacks on Sir John after their products were taken off the shelves, he revealed.

“I don’t know why those tests were ever sold on the high street,” he said. “They were using finger prick blood on tests designed to be used in the lab, and that should not have happened. They had to be taken out of the shops.

“And a lot of those guys were taking potshots at me because they didn’t like it.

“I understand the private labs feel a bit betwixt and between, and it’s hard to interpret decisions one day to the next. But I don’t think it’s quite as illogical as it looks.”

Despite the setbacks, Public Health England has since validated two accurate tests produced by the pharmaceutical giants Roche and Abbott, although some scientists and private labs have questioned whether the tests are any more effective than their rivals.

More than 100,000 NHS and care home staff have had their blood analysed since May, with the results fed back to individual health chiefs.

Do antibodies really protect us?

But Sir John, his team, and countless other scientists across the world are yet to answer the most crucial question, namely whether having Covid-19 antibodies actually protects a person from being reinfected. The three major studies currently underway which hope to answer that question are expected to see some results by the autumn, he said.

“These studies are what the UK is really good at, let me tell you, much better than anybody else. The Americans don’t have any of these studies,” Sir John said.

“But until we have answers, the test’s only utility is to tell people whether they've had the disease, not whether they’re protected from another wave of the infection.

“It’s useful in an analytical sense so that we can see the spread, but it’s no use to the man on the street.

“Everybody wants these tests, and people are saying ‘I wonder if that cough I had in March with a fever was actually Covid?’ And as a result, they want an antibody test to see whether that’s true or not. But it’s actually not much help yet in terms of returning to normal life.

And until it can be proved that antibodies confer protection, all talk of the “famous immunity passports” will have to wait, Sir John added.

Close to a breakthrough

So far every ten minute ‘lateral flow test’ (where finger prick blood is fed through a pregnancy-style cassette at home) tested by Public Health England (PHE) has been found wanting. The only validated options are so-called ELISA tests, where blood is taken intravenously by a medical professional and then analysed in a lab, which of course takes time.

However, Sir John believes his team are on the brink of a breakthrough.

Last week PHE launched a study into the effectiveness of a number of home testing kits, including one developed by the Rapid Test Consortium, involving Oxford University and four UK manufacturers: BBI Solutions, Abingdon Health, CIGA Healthcare and Omega Diagnostics. The results are due in late summer.

“We know the analytical quality is good,” Sir John said.

“All we need is the science that supports the notion that having antibodies is protection. We’re doing those experiments at the moment, and we’re doing them alongside T-cell studies.

“All I can say is we hope and think this Rapid Test Consortium test is the real deal, a game changer, if you like,” Sir John said.

“I foresee an antibody test appearing before the end of the year, and this may well be the one we’ve been waiting for."