(ORDO NEWS) — An international team of scientists decided to assess the consequences of the unprecedented number of mutations found in the new strain of coronavirus and the effectiveness of antibodies against past variants of SARS-CoV-2.
A team of scientists from the Swiss company Humabs BioMed and the American Vir Biotechnology, the University of Washington (Seattle, USA), as well as Italy, Argentina, Pakistan and Japan have identified antibodies that, unlike others, remain almost unchanged when exposed to the omicron strain and, therefore , can neutralize it.
The results of the study were recently reported in the journal Nature (the editors made a reservation that the work was reviewed and accepted for publication on an urgent basis – due to the rapid spread of a new variant of the coronavirus – so adjustments are possible).
As is known, omicron, in comparison with the original strain, has 37 amino acid substitutions in the S-protein, 15 of which are in the receptor-binding domain (RBD). This unusually large number of mutations raises concerns, as the vaccines so far available will be less effective against this variant than antibodies. In addition, such changes are believed to explain why the omicron strain was able to quickly disperse around the world – there are cases of infection in at least 100 countries – and infect people who have been vaccinated or have previously had Covid-19.
The authors of the work constructed a non-replicating pseudo virus that produces S-proteins on the surface of the viral particle, like coronaviruses. Then the scientists obtained pseudo viruses, the spike proteins of which contained mutations of the omicron strain or previous variants.
As it turned out, RBD “omicron” binds to the human membrane protein ACE2 ( angiotensin converting enzyme 2 ) with increased affinity, 2.4 times better – compared to the Wuhan strain (Wuhan-Hu-1) – and binds to murine ACE2.
The researchers further analyzed how effective antibodies against earlier versions of SARS-CoV-2 are in protecting against the new strain. “We observed a marked decrease in the neutralizing activity of plasma against omicron compared to the ancestral pseudo virus in the recovered and vaccinated, but the decrease was less pronounced after the third dose of the vaccine,” the paper says.
It turned out that most of the monoclonal antibodies (mAbs) targeting the receptor binding motif (RBM) RBD lost their neutralizing activity against the omicron variant in vitro : only three of the 29 mAbs retained unchanged activity, including the S2K146 antibody. In addition, sotrovimab, S2X259 and S2H97 – monoclonal antibodies that neutralize sarbecovirus, the so-called relative of SARS-CoV-2 – also neutralized omicron by recognizing antigenic sites outside the RBM. Sotrovimab activity decreased two to three times.
As the scientists note, by identifying the targets of such “broadly neutralizing” antibodies, it is possible to create vaccines and treatments that will remain effective not only against the omicron strain, but also against future variants of the coronavirus. “Monoclonal antibodies that recognize RBD epitopes, ‘conservative’ for different variants of SARS-CoV-2 and other sarbecoviruses, are likely to be the key to controlling the current pandemic,” the researchers said.
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