Monoclonal antibodies are back in the news. Governor Greg Abbott has just received an infusion after testing positive for Covid. The University of Mississippi Medical Center has opened a field hospital in its parking lot due to the increase in Covid cases. Half of their field hospital is a dedicated monoclonal antibody infusion center. Florida Governor Ron DeSantis is setting up similar centers and pushing people in his state to get the IVs as well.
The infusion process works best at the onset of an infection and takes a few hours to complete completely. They keep you for about an hour after the treatment to make sure you don’t have a bad reaction, which is very rare. These infusions are very effective in reducing the risk of hospitalization and death from Covid. Like vaccines, which work much better, this treatment is free, although monoclonal antibodies are often very expensive.
Monoclonal antibodies have been around since the late 1970s and their production won a Nobel Prize in 1984. Today they are booming in the pharmaceutical field and help many people with a wide variety of disorders. They have strange names like adalimumab, trastuzumab, galcanezumab, and ustekinumab. Their story involves the fusion of cancerous B cells with normal cells, immortality, animal models, selective growth media, and some genetic tricks to humanize them. I have written about them in previous articles and will forgo the full review. However, if you missed them, I suggest you watch a video by John Nguyen called “Monoclonal Antibody Production”. You can find him and a few others that he created by searching for his name on YouTube.
Regeneron makes the most widely used monoclonal antibodies against SARS-CoV-2. Regeneron scientists painstakingly searched libraries for antibodies that bind to the SARS-CoV-2 spike protein. After careful research, they chose two antibodies (REGN10933 and REGN10987) that bind very tightly to different regions of the receptor binding domain (RBD) of viral spike proteins. RBD is the part of the virus that must adapt to the ACE 2 receptors in your cell in order to enter and replicate. Blocking the RBD would stop the virus.
The genius of Regeneron is that they know the virus can mutate. Natural selection would favor any virus that can avoid being bound by their manufactured antibodies. Previous research has shown that SARS-CoV-2 can evolve quickly to avoid a single monoclonal antibody, and many of our newer variants can prevent certain antibodies from binding to it. However, it is less likely to detect mutations to avoid multiple monoclonal antibodies attached to different regions of spike proteins. Understanding Darwin’s game is key, and it’s obvious they do.
If you like the details, I suggest a few free journal posts. The first is titled “Studies in Humanized Mice and Recovering Humans Produce Cocktail of SARS-CoV-2 Antibodies”. The second is titled “Antibody Cocktail Against Spike Protein of SARS-CoV-2 Prevents Rapid Mutational Escape Observed with Individual Antibodies”. These are the first two articles focusing on monoclonal antibody research in August 2020. In March, a more recent article published in “Nature” was titled “Antibody resistance of variants B.1.351 and B.1.1.7 of the SARS-CoV-2 “. It scares me a little and shows how this virus evolves to escape antibodies. Still, a sentence towards the end gave me some hope: “The activity of REGN10933 is impaired, although its combination with REGN10987 retains much of the neutralizing activity. “
Dr Jack Brown is the President of the Science Division of the Collège junior de Paris. His scientific articles are published every Sunday.