Study Identifies Potential Therapeutic COVID-19 Antibody

An antibody isolated from a patient who recovered from severe acute respiratory syndrome (SARS) in 2003 could be a potential therapeutic COVID-19 antibody, according to a study recently published in Nature.

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The study, entitled “Cross-neutralization of SARS-CoV and SARS-CoV2 by a human monoclonal antibody,” explains the identification and characterization of the antibody categorized as S309. The study was conducted by researchers at Vir Biotechnology, Inc., clinical-stage immunology company developing therapeutics for COVID-19.

“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,” Herbert “Skip” Virgin, MD, PhD, chief scientific officer at Vir, said in an announcement. 

“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.”

Human antibodies can potentialy neutralize SARS-CoV-2 and related viruses, suggesting a high barrier to resistance. Antibody testing looks for antibodies to the virus and can help identify individuals who have developed an adaptive immune response.

Researchers at Vir used cyro-electron microscopy and binding assays to show that S309 recognizes a “glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment.”

S309, along with other antibodies identified, further enhances SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants.

To evaluate the neutralization potency of the SARS-CoV-2 monoclonal antibodies (mAbs), researchers carried out pseudovirus neutralization assays using a murine leukemia virus (MLV) pseudotyping system. 

S309 showed comparable neutralization potencies against both SARS-CoV and SARS-CoV-2 pseudoviruses and has the ability to neutralize all SARS-CoV-2 to date and possibly many other related coronaviruses. 

The data also proved that the use of mAbs combinations can prevent or control the SARS-CoV-2 pandemic by providing immediate protection and complementing the development of prophylactic vaccines.

Accelerated development of mAbs in a pandemic setting could be reduced to five to six months compared to the traditional timeline of ten months to a year.

“The recent finding that ansuvimab (mAb114) is a safe and effective treatment for symptomatic Ebola virus infection is a striking example of the successful use of mAb therapy during an infectious disease outbreak,” Vir researchers said in the study. 

“We previously isolated potently neutralizing human mAbs from memory B cells of individuals infected with SARS-CoV24 or MERS-CoV25. Passive transfer of these mAbs protected animals challenged with various SARS-CoV isolates and SARS-related CoV (SARSr-CoV), as well as with MERS-CoV.”

There are over 1.5 million cases of coronavirus across the country. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread. 

At the beginning of April, GlaxoSmithKline (GSK) and Vir announced a collaboration to enhance COVID-19 drug discovery through the use of CRISPR and artificial intelligence.

The partnership initially focused on accelerating the development of specific antibody candidates using Vir’s monoclonal antibody platform technology and GSK’s expertise in functional genomics. 

Vir’s platforms, VIR-7831 and VIR-7832, have already shown a similarity for the SARS-CoV-2 spike protein and researchers believe they show great potential to neutralize the SARS-CoV-2 sequence.  

“Vir’s unique antibody platform has precedented success in identifying and developing antibodies as treatments for multiple pathogens, and it is highly complementary with our R&D approach to focus on the science of immunology,” Hal Barron, MD, chief scientific officer and president of GSK, said in the announcement.