Last year, scientists at Scripps Research and Toscana Life Sciences examined the blood of 14 COVID-19 survivors to discover the most powerful antibodies against the SARS-CoV-2 virus. One of the most powerful molecules that emergednow in stage II/III trials in Italy was an antibody called J08, which seemed to be capable of preventing and treating COVID-19.
The same groupa collaboration between Scripps Research and in Italy and France has shown exactly how J08 binds to different SARS-CoV-2 variants in different conformations, implying that the J08 antibody, owing to its flexibility, will likely remain effective against future COVID-19 variants.
Understanding the details of J08 proves what works against the virus, and maybe how we can make antibodies even more powerful, according to senior authorAndrew Ward, PhD, of Scripps Research.
When a person is exposed to a virus like SARS-CoV-2, their body generates a wide spectrum of antibodies that bind to different sections of the virus to remove it from the body. Scientists who are considering vaccines and treatments against COVID-19 are interested in how many naturally produced antibodies like J08 are effective. In the months following Ward and his colleagues examined J08, it became clear that the antibody, unlike many others, was effective against a variety of COVID-19 forms.
In the following experiments, researchers determined the three-dimensional structure of J08 as it ties to the spike protein of SARS-CoV-2. They discovered that J08 successfully hooked to the Alpha, Beta, Gamma, and Delta variants, and neutralized the viruses that hindered them from replicating. However, J08 became approximately 7 times more slowly, then rapidly came off. 4,000 times more J08 was required to fully neutralize Omicron SARS-CoV-2 compared to other versions.
With other Omicron variants, this antibody quickly binds quickly and fails to come off for hours and hours, according to co-first author Gabriel Ozorowski, a senior staff scientist at Scripps Research. At first sight, with Omicron, we discovered that it still binds, but it falls off very quickly. The two structural issues have been identified.
J08 is linked to a very small area of the virusa section that generally remains unchanged as the virus mutes. Moreover, J08 may be placed in two completely different positions, like a key that attempts to open a door from the side up or downward.
This small, flexible footprint is part of why J08 is capable to cope with so many mutations and they do not affect the antibody binding unless they happen to be in this one very small part of the virus, according to Jonathan Torres, the lab manager at Scripps Research.
The Omicron variation of SARS-CoV-2 was characterized by two mutations (known as E484A and Q493H) that altered the tiny area of the virus that directly links with J08, allowing it to be strengthened if only one mutation is present. However, mutations in both are making it less effective against the Omicron version.
The findings, according to the researchers, support the continued clinical trials of the monoclonal antibody based on J08.
At the same time, I think I was really optimistic that future versions will not necessarily have both of these two critical mutations like Omicron, according to Ozorowski, so we are hopeful that J08 will continue to be extremely effective.