VIR-7831 Maintains Neutralizing Activity Against the SARS-CoV-2 California Variant
California-based Vir Biotechnology, Inc. announced new preclinical research demonstrating the ability of VIR-7831, the company’s investigational SARS-CoV-2 virus monoclonal antibody (mAb), to maintain its neutralizing activity against a mutation in the receptor-binding domain (RBD) of SARS-CoV-2, called L452R.
L452R has been found in the California SARS-CoV-2 variant (B.1.427/B.1.429).
Study results also demonstrate that the L452R mutation reduced the neutralization potency of plasma from vaccinated and convalescent donors and the neutralization activity of 14 RBD-specific and 10 N-terminal domain (NTD)-specific monoclonal antibodies, including three clinical-stage mAbs.
Non-peer-reviewed data was published on April 1, 2021, and submitted to a peer-reviewed journal for future print publication.
In this new study, researchers at Vir and the University of Washington report the rapid and exponentially increasing spread of the California variant throughout all 50 states and in 29 additional countries worldwide and characterize the impact of its three mutations: S13I and W152C in the NTD and L452R in the RBD.
Data from 43 vaccinated donors and nine convalescent donors demonstrated that, in a pseudotyped virus system, the S13I, W152C, and L452R mutations reduced the neutralization potency of plasma by three to sixfold.
The L452R mutation reduced the neutralization activity of 14 out of 35 RBD-specific mAbs, including three clinical-stage antibodies. Researchers also observed a complete loss of neutralization by all NTD-specific mAbs mediated by an unconventional escape mechanism. VIR-7831, which targets a non-receptor binding motif (RBM) epitope, was unaffected by the L452R mutation.
“The rapid increase in the frequency of this variant in California and neighboring states and its ability to confer some degree of resistance to vaccines and antibody therapies is concerning,” commented David Veesler, Ph.D., associate professor of biochemistry, the University of Washington in Seattle, in a press statement.
“The reduced sensitivity of this variant to plasma antibodies results from three individual spike mutations that mediate evasion from both RBD (partial) and NTD (total) specific antibodies. Together, these data demonstrate that if we are to combat current and anticipated future variants, there is a critical need for monoclonal antibodies that target invariant regions of the spike protein with the potential for a high barrier to resistance.”
VIR-7831 is an investigational compound not approved by the U.S. Food and Drug Administration or any other regulatory authority.
Vir Biotechnology is a clinical-stage immunology company focused on combining immunologic insights with cutting-edge technologies to treat and prevent serious infectious diseases.