How did the antibodies to the coronavirus
A study on human monoclonal antibodies to coronavirus has been reviewed
Alexandra "Renoire" Alekseeva, XX2 century
In March, a preprint of an article was published on the bioRxiv website, the authors of which found human monoclonal antibodies that neutralize the new coronavirus. The study was conducted by scientists from the University of Utrecht (Universiteit Utrecht) in collaboration with the Erasmus University Medical Center (Erasmus MC) and the pharmaceutical company Harbour BioMed. It makes sense to treat the research at the preprint stage with a certain degree of caution, but this work passed through the review filter and was published in early May in the journal Nature Communications (Wang et al., A human monoclonal antibody blocking SARS-CoV-2 infection). Let's talk about it in more detail, as it gives hope for the development of a drug.
Antibodies are proteins synthesized by plasma cells. They are part of the secondary immune response to the pathogen. The antibodies bind to the pathogen protein, the antigen, and thus can neutralize the harmful microbe. Scientists have been able to massively create antibodies specially tuned to interact with a certain antigen for some time. In another way, these antibodies are called monoclonal, since they are produced by cells belonging to the same cell clone. Such antibodies can be produced in large quantities in the laboratory – it is enough to merge the B-cell producing the desired antibody and the myeloma cell to get a hybridoma – an antibody-creating cell capable of multiplying indefinitely. Monoclonal antibodies can be used for various purposes, for example, in the development of diagnostic tests or even for the treatment of patients. There are, for example, drugs for the treatment of Ebola based on monoclonal antibodies.
The viruses SARS-CoV-2, which causes COVID-19, and SARS-CoV, the causative agent of SARS, belong to the subgenus Sarbecoviruses of the Coronavirus family. On the surface, they have spike-like proteins that bind to the ACE2 receptor (angiotensin converting enzyme) of infected human cells and thus ensure the penetration of the pathogen's genetic material into the cell. The spike-like proteins of SARS-CoV and SARS-CoV-2 are very similar in structure, 77.5% of their amino acid sequence is the same. One of the ways to neutralize the virus is to prevent the binding of spike proteins to the ACE2 receptor. And here monoclonal antibodies can help, potentially preventing the binding of the spike protein and the ACE2 receptor.
This is how the antibody is schematically depicted. The letter Y is formed by so-called heavy chains, and light chains are attached to the branches of Y. The constant domain is indicated in blue, and the variable domain is indicated in yellow, which adapts to one or another antigen.
The study was conducted as follows: first, 51 B-leukocytes were detected in H2L2 mice vaccinated against the pathogen.
H2L2 – transgenic mice, specially "designed" so that their B cells produce antibodies, in which the constant domains of the heavy and light chain were like mice, and the variable domains were like humans. For more information about this, follow the link (Eng.).
Further, hybridomas of these cells were obtained and propagated in bioreactors. Then the sediment was sifted out, and 51 samples of the liquid containing antibodies were tested using enzyme immunoassay (ELISA), as a result of which four types of cells producing antibodies effective against the new coronavirus were identified. And one of these four types, 47D11, produced antibodies effective against both SARS-CoV and SARS-CoV-2. Then the chimeric antibody 47D11 H2L2 was converted into a completely human one – variable domains were "hung" on the constant domains of the light and heavy chains of the IgG1 type, as in the chimeric antibody 47D11 H2L2. Then this antibody was sent for testing, in which it was shown that 47D11 acted on both viruses and prevented infection from entering the cell on a Vero cell culture.
"47D11 binds to the preserved epitope at the binding site of the spike receptor, and this explains its ability to simultaneously neutralize both SARS-CoV and SARS-CoV-2," the authors of the study comment.
Preserved (preserved, conserved) epitopes inside each viral protein are regions with minimal polymorphon activity and at the same time with strong epitope activity, allowing the same antibodies to recognize different closely related viruses. Given the high frequency of virus mutations, it is advantageous to create antiviral vaccines aimed specifically at conservative epitopes of viral proteins.
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