Vir Biotechnology Publishes New Research Characterizing Variation in the SARS-CoV-2 Spike Protein and Virulence of a Prevalent Immune Evasion Variant, N439K - Seite 2

Based on a review of sequenced viral isolates from 1,918 Scottish patients and clinical outcomes for 1,591 of these patients, N439K demonstrated similar clinical virulence to the wild-type 439N strain, full replication in the upper respiratory tract, the capacity to replicate in cultured cells, and the ability to effectively compete in in vitro growth assays with the wild-type virus. These data demonstrate that the virus exhibits fitness despite a mutation in the RBM.

To understand whether and how the N439K mutation might evade immunity, researchers noted that the binding of polyclonal sera to SARS-CoV-2 spike was reduced by the mutation in a sizeable fraction of the 445 samples obtained from recovered individuals. Additionally, out of 144 human neutralizing mAbs isolated from individuals who recovered from SARS-CoV-2 infection early in the pandemic, a significant number failed to efficiently recognize N439K. When tested across four clinical-stage antibodies – S309 (the precursor of VIR-7831), LY-CoV555, REGN10933 and REGN10987 – S309, which targets a non-RBM epitope, LY-CoV555 and REGN10933 were capable of neutralizing the N439K variant.

“These data provide critical evidence that more immune-evasive SARS-CoV-2 variants are likely to emerge, necessitating the updating of vaccines and the development of monoclonal antibodies that are highly resistant to viral escape,” said George Scangos, Ph.D., chief executive officer of Vir. “This is what we had in mind when we designed VIR-7831. By targeting a highly conserved epitope with the potential for a high barrier to resistance, we hoped to evade ongoing mutations and increase the long-term immunity of people exposed to SARS-CoV-2. We look forward to continuing to evaluate the utility of VIR-7831 in the prevention and treatment of COVID-19.”

This study was conducted in collaboration with Professors Emma Thomson, M.D, Ph.D., and David Robertson, Ph.D., and their teams at the MRC-University of Glasgow Centre for Virus Research.

As part of Vir’s ongoing commitment to addressing the COVID-19 pandemic, Vir scientists continue to publish new research designed to enhance the scientific understanding of SARS-CoV-2 and COVID-19. The Company’s most recent publications highlight:

• The mechanisms and risk for antibody-mediated enhancement of disease (Nature, October 2020);
• The identification and characterization of ultra-potent anti-COVID neutralizing mAbs (Science September 2020);
• The nature and half-life of human anti-SARS-CoV-2 antibodies in recovered individuals (Cell, September 2020). This research also showed that the part of the SARS-CoV-2 spike that contains the N439K mutation is a dominant target of the antibody response in many individuals;
• A mAb, S309 (the parent of VIR-7831 and VIR-7832), that covers both SARS-CoV-1 and SARS-CoV-2, which may be useful for the current and future pandemics (Nature, May 2020); and
• How to engineer mAbs with significantly increased efficacy in the treatment and prophylaxis of respiratory viral infections (Nature, April 2020).