Test to reveal how COVID-19 vaccination affects each person’s immune system

Disease and treatment 17. dec 2020 2 min Clinical Professor Peter Garred Written by Morten Busch

While we wait for the vaccines that can help us escape the clutches of the COVID-19 pandemic and its resulting lockdowns and millions of deaths, a debate is in full swing worldwide. Are vaccines dangerous? Do they work? Should I get vaccinated? A new antibody test shows what types of antibodies people with COVID-19 develop, and the researchers linked this with their severity of illness. The test may also reveal which antibodies a vaccine creates in each individual and thus also whether the vaccine works or not.

The scourge of the COVID-19 pandemic will not be eliminated until most of the world’s population develops antibodies against SARS-CoV-2. Herd immunity can be achieved if enough people have the right antibodies at the same time, because viruses need a susceptible host. Whether you have been infected with SARS-CoV-2 or you get vaccinated, each person’s immune system will develop slightly different types of antibodies and thus different ways of combatting COVID-19. A new test can reveal the types of antibodies each person has developed.

“Most existing antibody tests tell you whether you have developed antibodies but not what type. This is important knowledge, since the type of antibodies is crucial to determining whether your immune system can defend you against new virus attacks the next time. By examining antibodies among 350 people who got COVID-19 in the spring, we found that the type and number of antibodies are associated with the severity of disease. The new test enables us to test people who have had COVID-19 or have been vaccinated and is an important step in understanding how we become immune to SARS-CoV-2,” explains Peter Garred, Clinical Professor, Diagnostic Center, Rigshospitalet and Department of Clinical Medicine, University of Copenhagen.

The most severely ill people appear to be better protected

The new antibody test further refines the test the researchers from Rigshospitalet in Copenhagen developed during the first wave of the pandemic. The sandwich ELISA test tracked transmission well by determining whether a person has had COVID-19 or not. The new, more advanced test is called a direct ELISA-based assay.

“The new test enables us to distinguish which of the immunoglobulin types IgM, IgA and IgG are present in the bloodstream. Different immunoglobulins provide different kinds of immunity, so while the sandwich ELISA test is ideal for tracking transmission in the community, this direct test can be used to examine the types of antibodies in the blood over time,” explains Peter Garred.

The immunoglobulins are small proteins the immune system uses to recognize microorganisms. When a person has been attacked by a bacterium or a virus or has been given a vaccine, the immune system stores information so that it can react quickly the next time the person is exposed. This means that the person has become immune.

“There are five types of immunoglobulins, and the new test can measure the three most important ones. We can measure IgM, which the immune system uses in immediately responding to external threats; IgA, which is most important on the body’s surfaces and mucous membranes, where it combats intruders to prevent them from entering; and then IgG, which is present in blood serum, where it can recognize and detect threats that have entered the body,” says Peter Garred.

The researchers examined 350 people who had COVID-19. They then used the new test to measure the quantities of the various types of antibodies 11 weeks after infection and determined whether the severity of COVID-19 was associated with the antibodies developed.

“The study showed that the IgM, IgA and IgG response to SARS-CoV-2 is significantly correlated with the severity of the disease. The more ill you get, the greater the antibody response, and those who had a more severe illness trajectory had especially more IgG,” explains Peter Garred.

Testing whether a vaccine works

Since IgG typically stays in the body longer than IgM, the results suggest that people who have had a severe illness trajectory will also have greater protection over a longer period of time, but the researchers cannot be certain yet.

“Based on our test set-up, we have also developed a neutralization assay that specifically measures the extent to which the antibodies in the blood of each person can neutralize SARS-CoV-2. Once this is fully tested, we can then use it to measure whether a person is protected against COVID-19 in the future,” says Peter Garred.

The new type of assay may also prove to be a very effective way of testing the upcoming rollout of vaccines, because each person’s immune system will also react differently to a vaccine similarly to how it reacts to SARS-CoV-2 infection.

“This means that we can investigate whether vaccines against SARS-CoV-2 actually create a protective antibody response and measure how this changes over time. All this will indicate how strong each person’s immunity is, so you know whether you can feel safe, and if the result is not positive, you know that you are not immune and may need another type of vaccine,” concludes Peter Garred.

SARS-CoV-2 antibody responses are correlated to disease severity in COVID-19 convalescent individuals” has been published in the Journal of Immunology. The new antibody test was developed in a collaboration between Rigshospitalet, the University of Copenhagen and Novo Nordisk A/S, with support from the Carlsberg Foundation. In 2020, the Novo Nordisk Foundation awarded a grant of DKK 4,802,750 to Peter Garred for the Copenhagen SARS-CoV-2 Antibody Testing Initiative.

Peter Garred leads a research group at Rigshospitalet and the University of Copenhagen. He tries to understand the structure, molecular genetics and c...

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