One trillion possibilities is to quickly detect potent COVID-19 monoclonal antibodies

Scientists at the University of Pittsburgh School of Medicine have found the fastest way to identify the powerful human monoclonal antibody neutralizing Sarv-Cov-2, the virus that causes COVID-19.

This method – as well as a trio of successful animal studies on antibodies, now called “AB1” – Proceedings of the National Academy of Sciences. AB1 is on track for human medical tests early next year.

At any given time, the human body has up to 10 billion different antibodies. With samples from several hundred people, senior author Dmitry Dimitrov, Ph.D., director of the Pitts Center for Antibody Therapeutics (CAT), and his team have built multiple libraries with a total of 1 trillion human antibodies over the past several years. With such a large number, the hurdle is that these libraries have effective antibodies against any pathogenic disease – the challenge is to identify the right antibodies in the libraries that the Pitt team has mastered.

“Building a variety of antibody libraries is an art,” said John Mellors, MD, co-author and head of the Department of Infectious Diseases at Pete and UPMC. “Not everyone can do that. Dr. Dmitrov and his team not only identified potential therapies in record time, most Americans were also aware that the epidemic was flourishing, but by publishing their method, they prepared the world better for the future. Emerging diseases. “

In contrast, the main method used this year to identify antibodies neutralizing CARS-COV-2 was to detect patients who recovered from CoVID-19, isolate their cells that produce antibodies against the virus, and It produces antibodies from cells. A large number of antibodies must then be detected to find those that bind very tightly to the virus, which adds more time to the detection process. So when the Pete team identified AB1 back in February, the big companies didn’t have their monoclonal antibodies until the end of March or the beginning of April.

When Chinese scientists Aniko published the genetic sequence for SARS-Cavi-2 in January of this year, Dimitrov’s team quickly created the virus’s receptor-binding domain – part of the spike protein that binds to human cells – and used it as a “bait” Is taken. Many libraries of monoclonal antibodies. Dimitrov decided to focus only on the receptor-binding domain as a bait because his team was the first to identify the original SARS outbreak in 2003 and showed that it is the most important part of the spike protein to attract powerful neutral antibodies.

Like prosecutors trying to find gold in muddy rivers during the California Gold Rush, Dimitrov’s team quickly set up their libraries against spike protein receptor binding domains in February, quickly washing out useless antibodies and blocking highly promising candidates, who are wireless. Binding to the ACE2 receptor. The team struck “gold” in just six days.

AB1 is a complete human monoclonal antibody that binds to viruses, neutralizing SARS-CoV-2, infecting human cells. In tests on hamsters, regular rats and mice genetically engineered to express the human ACE2 receptor – the entry point of SARS-CoV-2 into cells 1 AB1 was very effective in preventing and treating COVID-19 or its animal analogues. AB1 is currently in production and could be added to Operation Warp Speed ​​or other human medical tests in early January 2021.

“The main difference between our fast‘ panning ’method and the‘ screening ’process used by most companies to detect antibodies against SARS-Covy-2 this year is that panning is much faster than screening, and we shouldn’t wait for that. Infected patients recover and make antibodies, ”Dimitrov said. “We found our monoclonal antibody in less than a week in February, which validated how well our pinging methods work. This will save valuable time in antibody therapy in people when a deadly virus comes out later.”

Last month, Mellors and Dimitrov announced the discovery of AB8, a small but very powerful antibody isolated from their antibody libraries by Wei Lee, Ph.D. Were performed by, assistant director of the Center for Antibody Therapeutics, who also discovered AB1. AB8 is not as advanced in development as AB1, but being a small molecule, it can potentially be powered by subcutaneous or inhalation, making it more practical for widespread use.