Würzburg. Immunologists from Würzburg are contributing to the groundbreaking Covid-19 study in Nature Medicine by investigating the binding ability of the antibodies. Elementary results: The human immune system must have seen the spike protein three times in order to build up broad immunity – also against omicron. The human immune system needs time for the antibodies to mature. The quality of the antibodies is at least as important as the quantity.
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Beta, Gamma and Delta and now Omicron. Since the beginning of the Covid-19 pandemic, new variants of concern, also known as VOC for variants of concern, have been developing. The big question that occupies researchers worldwide: How can we best protect people against SARS-CoV-2 infections?
A team led by Professor Dr. Ulrike Protzer from the Institute of Virology at the Technical University of Munich, Helmholtz Center Munich and the German Center for Infection Research and Professor Dr. Percy A. Knolle from the Klinikum Rechts der Isar of the TUM has now been published in the renowned journal Nature Medicine.
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Effective protection against variants
The scientists have shown that after a total of three contacts with the viral spike protein, the immune system develops a high-quality antibody response. These antibodies can also efficiently neutralize omicron. This applies to those who have recovered after two vaccinations and to those who have been vaccinated twice after a breakthrough infection as well as to those who have been vaccinated three times.
The researchers agree: “The immunity built up or strengthened by vaccination is the key to effective protection against future variants of the virus. But even a breakthrough infection, annoying as it is, achieves the effect of an additional vaccination.”
In the longitudinal study with 172 participants, the researchers determined several parameters in the blood of the test subjects: the amount of antibodies of the immunoglobulin G (IgG) type, the strength of the bond between the virus protein and the antibody, and the ability of antibodies to cause SARS -Neutralize CoV-2 variants in cell culture. The latter two are particularly important in estimating the level of protective immunity.
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Post from Würzburg
The immunologist Professor Dr. Martina Prelog and PD Dr. Giovanni Almanzar and medical doctoral student Tim Vogt from the University Hospital in Würzburg. To determine the binding activity of the antibodies against their antigens, they established and performed an avidity assay for SARS-CoV-2-specific antibody responses.
“We use the avidity to determine the synergistic binding strength of the antibodies,” explains Martina Prelog, using a graphic to illustrate this. This shows antibodies in the classic Y-shape that dock onto an antigen and neutralize it.
With a high avidity, the antibody-antigen bond holds even after an attempt at detachment by a so-called chaotropic agent.
“If in a serum sample of 1000 antibodies remain bound after treatment with a chaotropic agent, we have an avidity of 80 percent. We saw exactly this value in our serum samples. And that’s a really good value for high-binding antibodies,” notes Giovanni Almanzar, who tested several chaotropic agents to establish the investigations and developed the protocol for the avidity assays together with Martina Prelog.
strength of the immune system
“The strength of our immune system to neutralize the corona virus should not be measured solely on the basis of the concentration of the antibodies; the binding strength of the antibodies to the virus or its components is at least as important as the titer,” summarizes Martina Prelog.
The specialist in pediatric and adolescent medicine has been working on avidity for 15 years and has developed several immunological tests, including analyzes to determine cellular immunity for other infectious diseases.
When Ulrike Protzer asked us to carry out the antibody avidity analysis in mid-December, she immediately agreed. Everything was switched to examining these laboratory samples and within a few days almost 100 samples were analyzed with sera. And it goes further: “The avidity assay could also be a relevant method for determining the synergistic binding activity of the antibodies against their antigens in many infectious and immunological diseases in the future,” says Prelog. “Especially since the avidity matures through clonal hypermutation of the B cells and thus represents a surrogate marker for antibody maturation and immunological memory.”
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