California-based Vir Biotechnology, Inc. (NASDAQ: VIR) has announced a scientific publication detailing the discovery and characterization of a therapeutic antibody with protective activity against SARS-CoV-2 coronavirus infection. The antibody, S309, was used as the basis for the antibody candidates VIR-7831 and VIR-7832 that are currently being developed by Vir in partnership with GlaxoSmithKline (NYSE: GSK) for the treatment of COVID-19.
The article, “Cross-neutralization of SARS-CoV and SARS-CoV2 by a human monoclonal antibody,” was recently published in the journal Nature and provided an account of the methods used to identify and characterize S309, a neutralizing antibody clone isolated from a survivor of the 2003 SARS-CoV-1 pandemic and now under further development by Vir.
After isolating multiple monoclonal antibody clones from the patient’s memory B cells, long-lived antibody-producing white blood cells, the scientists used a variety of methods to distill their selection to the single clone that was best able to protect against infection by both SARS-CoV-1 and SARS-CoV-2, a strategic move since targeting highly conserved elements shared by both viruses could prevent the development of antibody-resistant virus strains.
The antibody clone, S309, was found to “potently” neutralize SARS-CoV-2 coronavirus by binding to the receptor-binding domain of the spike (S) protein, a structural element of the virus important for its engagement with and entry into human host cells.
The researchers demonstrated through binding assays and cryo-electron microscopy that S309 binds to a glycan-containing epitope of the coronavirus spike protein, and that cocktails of S309 and other protective antibodies could “further enhance SARS-CoV-2 neutralization.” The authors concluded that their results “pave the way for using S309- and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease.”
Chief Scientific Officer of Vir Dr. Herbert Virgin, MD, PhD, stated, “Remarkably, we believe S309 likely covers the entire family of related coronaviruses, which suggests that, even as SARS-CoV-2 continues to evolve, it may be quite challenging for it to become resistant to the neutralizing activity of S309.”
“In addition, S309 exhibits potent effector function in vitro, potentially allowing the antibody to engage and recruit the rest of the immune system to kill off already infected cells. We have seen in animal models of other respiratory infections, such as influenza, that effector function significantly enhances the activity of antibodies that are already potently neutralizing,” Dr. Virgin continued.
Vir’s Chief Medical Officer Dr. Phillip Pang, MD, PhD, stated “Potency, coupled with a high barrier to resistance, are hallmarks of a superior antiviral. We have seen this with mAb114, a single, potent monoclonal antibody that has been shown in a Phase 2/3 trial in the Democratic Republic of Congo to markedly reduce mortality from Ebola.” The monoclonal antibody mAb114 is currently being developed by Ridgeback Biotherapeutics and the National Institutes of Health.
According to Vir, since their antibody candidate VIR-7831, which was developed based on S309, binds to an epitope shared by both SARS-CoV-1 and SARS-CoV-2, it may be “more difficult for escape mutants to develop.” The antibody has been engineered to persist in the body for a more extended period of time and shown the ability to neutralize live SARS-CoV-2 virus in vitro. VIR-7832 has also demonstrated these properties but, in addition, could “potentially function as a T cell vaccine.”
While the passive administration of monoclonal antibodies is not intended to program the immune system to provide protection against the SARS-CoV-2 virus, as a vaccine is meant to achieve, it could contribute to the regulation of the pandemic until safe and effective protective vaccines become available.