20/07/2020 T-cells: the missing link in coronavirus immunity?

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T-cells: the missing link in coronavirus immunity? | Free to read
Evidence emerges that hard-to-measure cells are as vital as antibodies for conquering Covid-19

Clive Cookson, Anna Gross and Ian Bott in London JULY 18 2020

Scientists who have spent months focused on the role of antibodies in fighting
Covid-19 are beginning to suspect that a lesser known part of the immune system
is equally crucial: T-cells.

Evidence is emerging that T-cells, which can “remember” past infections and kill
pathogens if they reappear, have a big influence on how long patients remain
resistant to reinfection by Covid-19.

The cells, whose size and complexity dwarf tiny antibodies, also appear to affect
how well vaccines work and even the level of immunity in the community required
to suppress new waves of disease.

“Antibodies do look slightly precarious and transient in the blood, while there is a
lot of evidence that T-cells are long lasting,” said Mala Maini, professor of viral
immunology at University College London.

People who recovered from Sars, the disease most closely related to Covid-19, in
2003 still show cellular immunity to that coronavirus 17 years later.

T-cells, which circulate in the blood, might protect people who have been infected
and recovered from the new coronavirus but have no detectable antibodies shortly
thereafter.

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20/07/2020 T-cells: the missing link in coronavirus immunity? | Free to read | Financial Times

Immunity to any infection arises from a complicated interplay of different cells and
proteins such as antibodies, which are produced in various human tissues. Some
are designed to recognise invading germs. Others have the job of destroying them.

T-cells come in several different types, including killer T-cells, helper T-cells and
memory T-cells. Then there are B-cells — another essential category of white blood
cell. Among other roles B-cells are the immune system’s antibody factories.

Al Edwards, associate professor at Reading University’s School of Pharmacy, offers

an analogy. “T-cells are tasting the virus whereas the antibodies are feeling the
virus,” he said. “T-cells can promote antibody responses and antibody responses
can promote a T-cell response. These two systems work together.”

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20/07/2020 T-cells: the missing link in coronavirus immunity? | Free to read | Financial Times

“Even if you’re left with no detectable circulating antibodies, that doesn’t

necessarily mean you have no protective immunity, because you are likely to have
memory immune cells (B and T cells) that can rapidly kick into action to start up a
new immune response if you re-encounter the virus,” added Prof Maini of UCL.
“So you might well get a milder infection.”

Tom Evans, chief scientist at Oxford university’s vaccines spinout company

Vaccitech, said: “You can think of the human immune system as an orchestra
playing together and needing a co-ordinated performance from all the musicians
and their instruments. It doesn’t make scientific sense to talk about antibodies or
T-cells on their own.”

As data emerge from clinical trials of potential Covid-19 vaccines, the extent to
which they evoke T-cell immunity will be a focus of attention.

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20/07/2020 T-cells: the missing link in coronavirus immunity? | Free to read | Financial Times

Advocates of viral vaccines, which use a harmless genetically engineered virus to

carry coronavirus antigens into human cells, are already suggesting that their
method is more effective at raising a T-cell response than an alternative approach,
which injects coronavirus genes in the form of RNA or DNA into human cells.

More evidence is expected on Monday when Oxford scientists present the first
clinical trial results of their ChAdOx1 vaccine, which is based on a chimpanzee
adenovirus. But it remains to be seen whether the combination of neutralising
antibodies and T-cells raised by the vaccine will give strong and long-lasting
immune protection.

One reason why antibodies have been the

Latest coronavirus focus of attention is that they are far easier
news to measure in diagnostic tests than T-cells,
which are almost 10,000 times larger. The
trouble is that antibodies sometimes fade
fast, particularly in people who have had
mild or no Covid-19 symptoms, making
them an unreliable indicator of past
infection.
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“Antibodies are protein molecules
and the rapidly evolving
circulating in your blood, which can be
economic crisis here.
measured in a straightforward assay [blood
test],” said Herb Sewell, immunology
professor at the University of Nottingham.
“For T-cells, you have to extract them from the blood, keep them alive, and expose
them to the assay.”

Technology for mass testing of T-cell immunity is unlikely to be available in the

near future. However the first lab studies of the overall immune response to Sars-
Cov-2, the virus that causes Covid-19, are beginning to report results. One, led by
Jennifer Juno at the University of Melbourne and published in Nature Medicine,
studied 41 Australians with mild to moderate symptoms.

“Among the cohort, we found . . . a wide range of antibody responses,” she said.
“Some high and some low, but strong antibody responses were associated with . . . a
subset of a subset of the T-cells which were more effective at helping drive a better
antibody response.”

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20/07/2020 T-cells: the missing link in coronavirus immunity? | Free to read | Financial Times

Several studies suggest T-cells produced by other coronaviruses — which cause

only mild cold-like illness — may also recognise Sars-Cov-2 and provide some
protection against Covid-19.

This phenomenon may contribute to what some scientists have called

“immunological dark matter”, which could make herd immunity to Sars-Cov-2
achievable with an infection rate as low as 20 per cent, rather than the 60 per cent
level often cited. But the idea is controversial and much more evidence will be
required before it gains widespread scientific acceptance.

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20/07/2020 T-cells: the missing link in coronavirus immunity? | Free to read | Financial Times
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