An international team of immunologists, including members of the Department of Clinical Immunology and Allergology at Sklifosovsky Institute of Clinical Medicine (Sechenov University), published a paper on the properties of SARS-CoV-2 specific antibodies in the journal Allergy. Inna Tulaeva, who works at the Department of Clinical Immunology and Allergology, was among the authors.

The study found that antibodies to the correctly folded surface protein were required for the successful neutralisation of the coronavirus. ‘About 20% of the patients who recovered from COVID-19 do not develop protective immunity to the virus’, said Rudolf Valenta, the corresponding author on the paper. ‘The most important part of the immune response — which prevents the virus from attaching to the cells and invading them — is the formation of specific antibodies to the folded receptor binding domain (RBD) of the surface protein of the coronavirus. This protein fragment does not undergo significant changes during the mutation of the virus’.

The researchers used a microchip technology developed at the Medical University of Vienna (Austria). In this technique, large amounts of viral antigens were applied to a microscopic chip using a robot. In addition, overlapping protein fragments (peptides) of these antigens were applied to the chip, covering the entire spike protein — which harbours the RBD. This is the site through which SARS-CoV-2 binds to the ACE2 receptor of human cells.

The scientists found that antibodies from patients who had recovered from COVID-19 reacted only with the correctly folded RBD. It indicates the importance of the correct protein conformation — for diagnostic purposes and vaccine development.

The authors conclude that proteins used to diagnose the immune response to the coronavirus, as well as for vaccination, must be correctly folded. Peptides and linear forms of proteins are not effective for diagnostic purposes and vaccine development — and this explains the failure of many solutions proposed earlier. Also, people who sufficiently produce antibodies to the folded RBD are protected from coronavirus infection.

Last year, the same group of scientists developed a molecular test system for SARS-CoV-2 and investigated the immune status of patients who had recovered from mild COVID-19.

Read more: Gattinger P, et al. Neutralization of SARS-CoV-2 requires antibodies against conformational receptor-binding domain epitopes. Allergy (2021).