Antibodies protect against a wide range of COVID-19 virus variants – Washington University in St. Louis School of Medicine

The virus that causes COVID-19 today is not the same virus that first became ill in December 2019. Many of the variants currently in circulation are partially resistant to some of the antibody-based therapies developed based on the original virus. .. As the pandemic continues, more variants will inevitably emerge and the resistance problem will only grow.

Researchers at Washington University in St. Louis have identified antibodies that are highly protective at low doses against a wide range of viral variants. In addition, the antibody attaches to areas that are almost unchanged between mutants of the virus. This means that resistance is unlikely to develop here. Findings available online in the journal Immunity could be a step towards developing new antibody-based therapies that are less likely to lose their potency as the virus mutates.

“Current antibodies may work against some, but not all, mutants,” said the senior author. Michael S. Diamond, MD, PhD, Herbert S. Gasser, Professor of Medicine. “Viruses can continue to evolve over time and space. Widely neutralizing and effective antibodies that can function individually and combine to create new combinations can prevent resistance. I have.”

SARS-CoV-2, the virus that causes COVID-19, uses a protein called spikes to attach and invade cells in the airways of the body. Antibodies that prevent spikes from adhering to cells neutralize the virus and prevent disease. Many variants have acquired mutations in the spike gene that allow them to evade some of the antibodies produced against the original strain, compromising the effectiveness of antibody-based therapies.

To find neutralizing antibodies that act on a wide range of mutants, researchers began by immunizing mice with an important part of the peplomer known as the receptor-binding domain. Next, antibody-producing cells were extracted to obtain 43 antibodies that recognize the receptor-binding domain. In addition to Diamond, the research team included co-lead authors, staff scientists Laura Van Blargan and PhD. Lucas J. Adams, MD / PhD student. Staff Scientist Dr. Zhuoming Liu.Not just co-authors Dr. David Freemont, Professor of Pathology and Immunology, Biochemistry and Molecular Biophysics, and Molecular Microbiology.

Researchers screened 43 antibodies by measuring how well the original mutant of SARS-CoV-2 prevented the cells in the dish from being infected. Next, nine of the most potent neutralizing antibodies were tested in mice to see if they could protect animals infected with the original SARS-CoV-2 from disease. Multiple antibodies passed both tests, with varying degrees of efficacy.

Researchers have selected two antibodies that are most effective in protecting mice from disease and tested them against a panel of viral variants. The panel has all four mutants of concern (alpha, beta, gamma, delta), two mutants of interest (kappa and iota), and some unnamed ones being monitored as potential threats. It consisted of a virus containing a peaplomer representing a mutant strain. One antibody, SARS2-38, easily neutralized all mutants. In addition, a humanized version of SARS2-38 protected mice from disease caused by two variants of the virus, including the kappa and beta variants of the peplomer. It is especially noteworthy that SARS2-38 is not resistant, as beta mutants are notorious for being resistant to antibodies.

Further experiments identified the exact spots of the peplomer recognized by the antibody, and in principle two mutations that could interfere with antibody function were identified at those spots. However, these mutations are rare in the real world. Researchers searched a database of approximately 800,000 SARS-CoV-2 sequences and found escape mutations in only 0.04% of them.

“This antibody is highly neutralized (it works very well at low concentrations) and at the same time broadly neutralized (it works for all variants),” said molecular microbiology and pathology and immunology. Said Diamond, who is also a professor of. “This is a rare and highly desirable combination for antibodies. It also binds to unique spots of peplomer proteins that are not targeted by other antibodies under development. It is ideal for combination therapies. This antibody is elsewhere. You can start thinking about creating a combination therapy that is very difficult for the virus to resist in combination with another antibody that binds to. “