New, low-cost 'made in Spain' Covid immunity test ready to be rolled out

With the third dose of the Covid-19 vaccine approved for immunocompromised people, most of Spain's regional health authorities have already begun to administer the additional jab to some 100,000 affected people. The objective of the third dose is to reinforce protection for those with weakened immune systems who may not have responded sufficiently to the first two vaccines. 

But how is the immune response measured? 

There are several ways:

Measuring the immune-cellular response of people who have had the SARS-CoV-2 infection or have been vaccinated, in order to estimate how protected they would be in the face of a possible future infection (or reinfection), is complicated, hence the government's indecision about the real need for a third dose. However, a team of researchers from the Hospital Universitario de Canarias, led by immunologist Yvelise Barrios, has created a new, low-cost and easy-to-use test that offers reliable information on a person's immune response to Covid-19.

It is one thing to test whether or not we have antibodies (with serological tests) and another altogether to measure the neutralizing capacity of these antibodies. In addition, when the amount of antibodies generated after the vaccine or infection begins to decline, as has been seen to happen after six to seven months, it is necessary to look for T cells, which are the ones that activate memory B cells, which are those that in turn generate a more stable immune response in the body (they are the ones that activate the immune system to produce antibodies on the 'command' of the T cells).

Dr. Barrios' team has just presented the results of a new test developed, together with the allergist Víctor Matheu, that detects specific T lymphocytes for the Spike (S) protein of the new coronavirus.

As the Canary Island-based researchers explain, these tests are easy to perform, low cost and their reliability is practically 100%, as shown by the results obtained after tests with immunocompetent health personnel from the Hospital Universitario de Canarias, who had either had the infection or been vaccinated with the two doses of the Pfizer vaccine at least two weeks earlier. Now, six months after vaccination, they are re-evaluating the test with the first group. This test has also been tried out on personnel vaccinated with Moderna, Janssen, AstraZeneca and one person who received the Sputnik vaccine.

According to Barrios, the team is waiting for these results and the results from two other groups to be published in a scientific journal. One of the other groups was people with kidney transplants, who were tested five weeks after the complete vaccination process - "in immunosuppressed people, more time must be allowed for the immune response to be more vigorous and the evaluation to be better" - he explained, and in people with immunodeficiencies.

How does it work?

This test involves a harmless "pinprick" in the arm through which "a part of the S protein of the coronavirus manufactured in the laboratory is inoculated". "We are not putting live virus into the body", clarified Barrios. Then we wait for our skin to give us a reading. Within one to three days a small and localised reaction in the form of inflammation, redness or a little swelling at the site of the puncture will indicate that the T cells in the body are still "trained" to act against the coronavirus.

The test is very similar to those carried out for allergies, but modified to recognize SARS-CoV-2. "It is a delayed hypersensitivity reaction like the one used for tuberculin", explained the researcher.

As it can be used on a massive scale, this test could be "very useful" in deciding whether to administer booster doses to patients more vulnerable to Covid-19, such as the elderly who live in care homes. Several regional health authorities have already made a request to administer the tests, but central government is still waiting for more scientific evidence before approving its use.

Elderly nursing home residents were the first to start being vaccinated in Spain at the end of December 2020, followed by health workers caring for them, and those working on the front line against the pandemic. After more than nine months, it could be tthe case that many of these people currently present a low or non-existent level of antibodies, but that they retain an effective cellular response. This is precisely what this test measures and as such it has been received with "enthusiasm" by the scientific community and hailed as "very good news".

"It is more relevant that there are T cells than antibodies because antibodies are circulating proteins that diminish and disappear over time. On the other hand, specific T cells remain active much longer because that is where the immunological memory resides," Barrios explained. 

He also pointed out that they are "collaborating with a Canadian company with a view to its commercialisation", which he expects to reach the market in "a few months". Based on the result of this simple test a person would know if he or she needed a booster dose of the Covid-19 vaccine or not.

"What this test interprets is a cellular immune response, but we have not correlated our test with protection," Barrios clarified. "It is very important," he continued, "because until now, all the studies that have been done to measure the effectiveness of vaccines or to measure long-term immunity after having had the disease are based on antibodies and that is wrong. Furthermore, it means underestimating the immune response, which we know is based on T cells. "

This new tool could be used on a massive scale because it is "easy to interpret and perform", for example, researchers say, in nursing homes. "Now we are talking about third doses and we believe that in many cases an underestimation is being made of which people need these boosters because only antibodies are being measured. Cellular immunity is clearly underestimated", argues Yvelise Barrios.

Who is it suitable for?

The developers believe that this test would be "very useful" for institutionalised older people and for those with reduced mobility who have trouble getting to a hospital for a blood test. And not only for logistical reasons, but also because they are the sector of the population generating most doubts about vaccine protection.

"The test would also be very beneficial for babies and young children, from whom it is also difficult to draw blood, in order to see to what extent they develop natural immunity after having the disease, in many cases, asymptomatically, and also to see if they have been exposed to the virus," he added.

However, this test could be done by anyone who wants to know if they have an immune response to Covid-19.

The shortcoming of this new skin test, developed with "a lot of effort and little or no funding" is that its result is either positive or negative. It does not offer a scale of degree of cellular immunity against Covid-19. Cellular immunity is the specific response to a pathogen that has to be activated initially. Once T cells are activated, B cells are activated and antibodies are produced. It is different from the nonspecific and innate response, which always responds the same to microorganisms.

What does the EMA say about the third dose?

Last week, the European Medicines Agency (EMA) recognised that "the evidence is clearer on the need to consider additional doses" in immunosuppressed and elderly people, and stressed the need to accelerate and complete the vaccination of the general population against Covid-19.

However, EMA head of vaccine strategy Marco Cavalieri reiterated that "it is not clear" when to start considering a booster dose in the general population, because current evidence indicates that "vaccines offer high degree of protection" against hospitalisation, death and severe Covid-19 with all variants.

"From a health point of view, the priority should be to ensure that the maximum number of people are fully vaccinated (...) The evidence is increasingly clear on the need to consider additional doses for people who may respond poorly to the vaccine, such as those with severely depressed immune systems or some elderly patients," he stressed.