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Bengaluru doctors develop test to detect warrior T cells, could determine who gets vaccine first

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New Delhi: A team of doctors in Bengaluru has claimed to have developed a test that can examine specific T cell immunity for Covid-19.

The test promises to give a better picture of what percentage of the population has immunity to SARS-CoV-2 and also help identify those who should be prioritised for vaccination.

The team is now in the process of applying for a patent for the test, and will work with Professor Nagasuma Chandra of the Indian Institute of Science (IISc), Bengaluru, to analyse virus sequences specific to India and match the test to Indian population.

The test will need an approval from the Drugs Controller General of India to be used on people.

Dr Sonal Asthana of Aster CMI Hospital in Bengaluru, one of the doctors in the team that developed the test, told ThePrint that most of the discussion around Covid-19 immunity until a few weeks ago revolved around the presence of antibodies only.

As a result, a number of sero surveys have been conducted in cities, including MumbaiDelhi and Pune, which reveal what percentage of the population has been exposed to the virus and have developed immunity to it.

However, these surveys did not take into account those people who may have T cells that can protect them from Covid-19, even if they do not have detectable levels of antibodies.

But with this new blood test that can detect these T cells, the doctors hope to address this gap.

“We now know that the levels of antibodies start diminishing beyond six weeks. So those who are tested after a few months of being exposed to SARS-CoV-2 no longer have detectable levels of antibodies,” Asthana said.

“Over the last couple of months, the importance of T cell immunity has come forth. We realised that people who have been exposed to the virus have developed strong T cell response to the virus,” he added.

Body’s immunity response

The immune response to any kind of foreign pathogen in the body takes place in incremental steps. Immune system cells are primarily made up of leukocytes or white blood cells, which circulate through our body and scan for suspicious objects.

As soon as a body encounters a foreign pathogen, the first kind of immune system — known as the innate immune system — kicks in. It is non-specific, which means it protects against all pathogens the same way.

The innate immune response triggers the adaptive immune response, which is more specific to the kind of pathogen infecting our bodies. The adaptive immune response consists of T cells and B cells.

T cells produce memory cells that are capable of storing information about antigens. These cells take a few days to get triggered after the first instance of infection, but invoke a swift and efficient response the next time the pathogen is encountered.

B cells are the ones that produce antibodies or immunoglobulins to fight off an infection and help in recovery.

T cells are slightly more difficult to study than antibodies, Asthana said, which is why such tests are not available everywhere.

However, while the team claimed it to be a “first-of-its-kind” test, experts ThePrint spoke to said tests detecting T cells in the human body are already available.

The test

Working with Dr Vishnu Kurpad at Sri Shankara Cancer Hospital in Bengaluru, Asthana has developed a simple test for the assessment of specific T cell immune responses, which can be done at smaller labs without specialised equipment. The results can be obtained within 24 hours.

Chandra of IISc told ThePrint the test works by detecting the presence of T cells that are already primed to recognise the antigens of the SAR-CoV-2 virus.

If the blood has such T cells for the antigens, there will be a release of a protein called interferon-gamma. In the body, this protein plays an important role in inducing and signalling other parts of the immune response, she said, adding that essentially, the test looks for the production of this protein.

As part of the initial pilot study, blood samples from recovered, moderate and severe Covid-19 patients were analysed. Their studies showed that recovered individuals have high levels of cellular immunity as compared to hospitalised patients, Asthana said.

These tests will have a number of applications, including complementing serological surveys for antibody responses.

Understanding what percentage of the population has T cell immunity can provide a better picture of how far the community is from achieving herd immunity.

“We have also found that those with more robust T cell responses, suffer from a milder Covid-19 symptoms,” Asthana said.

Using this test, Covid-19 patients can be assessed and triaged based on which of them are more likely to develop symptoms.

The test can also be valuable for planning a vaccine programme.

“Whenever a vaccine becomes available, they need to be prioritised to a vulnerable group of people initially,” Asthana said.

Those who are antibody negative and have low T cell immunity would need vaccines early on.

Asthana said they still have additional work to do before their test can be turned into a marketable product.

The team is now preparing to carry out further tests according to protocols required to get approval from the Drugs Controller General of India, he added.

Chandra also said the team is now working on further improving the test.

“There can be minor changes in different viral strains. Some mutations could affect the proteins that are of interest to us in this research. If there is a protein that is not part of the virus circulated in India, even if there is an immune response to other proteins, our test may miss detecting those T cells,” she explained.

Test not novel, say experts

Tests detecting T cells in the human body are already available.

Satyajit Rath, an immunologist at IISER Pune, said the concept is not particularly novel. Such tests called interferon-gamma-release assays (IGRAs) are already available in the market for diseases like tuberculosis and cytomegalovirus infection.

He said tests for T cell responses use more complex protocols for several reasons.

“One reason is that, unlike B cell immune responses, which all end up, more or less, making antibodies, T cell immune responses have a large number of diverse outcomes — interferon-gamma is only one of them,” Rath told ThePrint.

“So, many different pathways have to be measured for assessing T cell immunity to SARS-CoV-2. An IGRA, like the one proposed, is unlikely to do all that,” he said.

“Another reason for complexity is that T cells recognise very short fragments of viral proteins. T cell responses to any viral protein are likely to be important. So, which viral protein/s one provides in the test is an important consideration,” he said.

Finally, in antibody assessments, there is at least the possibility of measuring “neutralising” antibodies, which is a measure of “immune protection”.

For T cell responses, there is no such correlation of protection, so it is much harder to interpret a ‘positive’ T cell response to SARS-CoV-2 in such a test, Rath said.

However, none of this is to say that such tests are useless or trivial, he added.

The print

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