https://scitechdaily.com/inescapable-covid-19-antibody-discovery-neutralizes-all-known-sars-cov-2-strains/
@biobook can you please give us the Plain English executive summary on this?
The surface of SARS-CoV-2 has a spike protein, with a tip called RBD (receptor binding domain) which binds to the ACE2 receptor on a cell of our lungs and thereby allows the virus to enter our cells.
This protein is made of about 1200 amino acids, strung together in a long chain, which then folds up to produce the spike-shaped molecule. During viral replication, mutations can occur, such that one or more of those amino acids are modified. If enough mutations pile up such that the virus now acts a little differently it may be considered a new variant of the original virus.
Many of those variants, like Delta, are still recognized well enough by the antibodies we make, but some are so different in one area, that our antibodies can’t recognize and neutralize them, and these viruses are called escape variants. Not that they’ve escaped from our bodies – quite the opposite – they’ve escaped from the stranglehold that our antibodies had on them, so they are now able to infect our cells and make us sick.
The scientists wanted to identify which areas of the spike are
least likely to mutate. Antibodies produced to those constant areas should be effective against any new variants, even though the spike may have mutations elsewhere. They found 45 different spike proteins from viruses related to SARS, but with slight differences in structure.
Next, they wanted to see how well different antibodies bind to these different spike proteins. They needed anti-spike antibodies of course, but these molecules can also have slight differences in structure. One antibody binds to one region of spike, and another binds to another region. One person may produce one anti-spike antibodies, another person produces slightly different anti-spike antibodies. The researchers isolated 12 anti-spike antibodies from the blood of people who had recovered from infection with either SARS-CoV2 or the related SARS-CoV in 2003.
When those 12 antibodies were exposed to the 45 spike proteins, all the antibodies bound to some of the spikes, but there was one superstar, an antibody that bound to the RBD on every single spike.
It turns out that when the 1200 amino acid chain folds up, there’s one area of the RBD that is hidden inside the structure, and is exposed only at the last moment when the Spike RBD begins to bind to the ACE2 receptor of our cells. The remarkable antibody they found zips in there and neutralizes the spike, blocking its ability to bind ACE2. This area of spike is unlikely to mutate, as evidenced by the finding that it exists in the spike proteins of all 45 different viruses that resemble SARS Cov-2.
To check whether this binding would be medically relevant, they injected the antibody into hamsters, and found that it protected them from SARS infection.
Till now, companies that develop monoclonal antibodies have searched for antibodies that would bind most
strongly to the spike protein. These authors suggest that they search for antibodies that bind
broadly, that is, that bind to a large variety of similar viruses, so that the antibodies would have a good chance of neutralizing any new variant that appears.
Based on an excellent article by Sabrina Richards,
https://www.fredhutch.org/en/news/center-news/2021/07/novel-coronavirus-immunity.html