Last year, scientists at Scripps Research and Toscana Life Sciences studied the blood of 14 COVID-19 survivors to find the most effective antibodies against SARS-CoV-2. One of the pioneering molecules that appeared – now in phase II / III trials in Italy – was an antibody called J08, which appeared to be able to prevent and treat COVID-19.
Now, the same group — a collaboration between scientists at Scripps Research and in Italy and France — has visualized exactly how J08 binds to different SARS-CoV-2 variants in different configurations, explaining what makes the monoclonal antibody so potent. Search published in Proceedings of the National Academy of Sciencesindicates that the J08 antibody, given its flexibility, will likely remain effective against future variants of COVID-19.
“Although we cannot predict which COVID-19 variants will emerge next, understanding the details of J08 reveals what works against the virus, and perhaps how we can engineer the antibodies to be more effective,” says senior author Andrew Ward, PhD, professor of structural biology. Computational integrative at Scripps Research.
When someone is exposed to a virus like SARS-CoV-2, their body generates a variety of antibodies that bind to different sections of the virus to remove it from the body. Scientists designing vaccines and treatments against COVID-19 are interested in what makes some of these naturally produced antibodies — such as J08 — more effective than others. In the months since Ward and his collaborators first identified J08, it became clear that the antibody, unlike many others, was potent against a variety of COVID-19 variants.
In the new work, the researchers determined the three-dimensional structure of J08 as it is bound to the SARS-CoV-2 protein. They confirmed that J08 was successfully linked to Alpha, Beta, Gamma and Delta variants and neutralized the viruses – preventing them from reproducing. However, the J08 attached to the Omicron variant about 7 times slower, and then quickly took off. About 4,000 times more J08 was needed to completely neutralize Omicron SARS-CoV-2 compared to the other variants.
“With variants other than Omicron, this antibody binds quickly and does not work for hours and hours,” says co-first author Gabriel Ozorowski, chief scientist in the Ward Lab at Scripps Research. “With Omicron, we were happy at first because we found it was still binding, but it’s declining very quickly. We’ve identified the two structural changes that are causing this.”
The team showed that for all variants, J08 binds to a very small portion of the virus — the section that generally remains the same even as the virus mutates. Moreover, J08 can be attached in two completely different directions, such as a key that can open the door whether it is right side up or upside down.
“This small, flexible fingerprint is part of the reason why J08 is able to tolerate so many mutations — it doesn’t affect antibody binding unless you happen to be present in this very small portion of the virus,” says co-first author Jonathan Torres, director of the Ward Laboratory in the US. Scripps Research.
However, the Omicron variant of SARS-CoV-2 contained two mutations (defined as E484A and Q493H) that altered the small region of the virus that interacts directly with J08, locking it in place. Ward and his collaborators found that if only one of these mutations is present, J08 is still able to strongly bind and neutralize the virus, but mutations in both make it less effective against the Omicron variant.
The researchers say the new findings support ongoing clinical trials of J08-dependent monoclonal antibodies.
“I think we’re pretty confident that future variants won’t necessarily have these two critical mutations at the same time as Omicron, and that makes us hopeful that J08 will continue to be very efficient,” Ozorowski says.
Protects the taste receptor from omicron infection
Emanuele Andreano et al, Highly potent human monoclonal antibodies from COVID-19 convalescent patients, prison cell (2021). DOI: 10.1016 / j.cell.2021.02.035
Jonathan L. Torres et al., Structural insights into a highly potent neutralizing human monoclonal antibody for SARS-CoV-2, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2120976119
Submitted by Scripps Research Institute
the quote: Scientists Explain What Makes the COVID-19 Antibody ‘J08’ So Powerful (2022, May 13) Retrieved May 15, 2022 from https://medicalxpress.com/news/2022-05-scientists-covid-antibody- j08-potent.html
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