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Approximately one in five people with corona disease do not develop immune protection against SARS-CoV-2, according to a study by scientists at MedUni Vienna. Protection requires the ability to form antibodies.
The protection that prevents docking and invasion of the body’s cells only occurs if antibodies can be formed against the folded receptor binding domain (RBD) of the spike protein. However, some people are unable to do so, likely due to current vaccines.
Corona sufferers and antibodies
This docking site does not change significantly even in viral mutants, a MedUni statement stressed Monday. An antigen-based vaccine targeting RBD could provide a remedy, but it is not yet available. A team led by Rudolf Valenta and Winfried F. Pickl of MedUni Vienna’s Center for Pathophysiology, Infectiology and Immunology had already shown a year ago, using an initial cohort of recovered Covid-19 patients with a mild course of the disease, that a considerable proportion of those infected were unable to form protective antibodies against SARS-CoV-2.
In the follow-up study now published in the journal Allergy, Valenta, an allergist and immunologist, and his team analyzed the antibody response of a larger cohort following mild and severe SARS-CoV-2 infection. The study was conducted using microarray technology developed at MedUni Vienna, whereby a large number of viral antigens are machine-deposited onto a microscopic-sized chip. In addition, overlapping protein fragments (peptides) of these viral antigens were fixed to it, covering the entire spike protein on which the receptor binding domain (RBD) is located. With this, SARS-CoV-2 virus binds to the ACE2 receptor of human cells.
Virus apparently needs three-dimensional folded protein
The researchers’ expectation was that there would be an immune response to the peptides, but antibody formation only occurred against the intact, three-dimensionally folded spike protein. Indeed, proteins acquire their three-dimensional shape through the physically induced process of protein folding. The SARS-CoV-2 virus apparently requires the three-dimensionally folded protein to dock with the body’s cells. Only an antibody response against the folded protein, but not against parts of it, protects against infection.
High antibody levels against the folded spike protein, and in particular against the RBD it contains, prevent the virus from binding to human somatic cells, it was concluded. However, if someone cannot form antibodies against the folded RBD, they have little protection. The researchers also showed that only the folded RBD, but not unfolded RBD, produces immune protection when immunized. Therefore, because the genetic vaccines currently in use mimic infection, it is possible that vaccine breakthroughs can be explained by a lack of development of antibodies to folded RBD.
Antibody production is not expected to work in all corona-genetics
People who produce sufficient amounts of antibodies against folded RBD are said to be protected against SARS-CoV-2 infection. These antibodies are readily measurable in the blood by neutralization tests. However, production of these antibodies does not function in twenty percent of the recovered – and probably vaccinated – population, he said. “The development of an RBD-based antigen vaccine boosted by helper protein is urgently needed. This would be highly effective in inducing RBD-specific and thus neutralizing antibodies, the levels of which could be kept high by booster vaccinations,” Valenta explained. This would also make it possible to exploit the “Achilles’ heel” of the virus, whose docking site does not change significantly with mutations, the physician emphasized.
- sources: vienna.at/APA/picture:pixabay.com
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