Vir Biotechnology, Inc. today announced the online publication of new research characterizing differences in antibody responses to SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2). This analysis, which is the largest to date, describes both the binding properties and kinetics of neutralizing antibodies, providing key insights that could be important to the development of new vaccines and therapies to address COVID-19. The results were published "online first” in the peer-reviewed journal Cell and will appear in the November 12, 2020, print edition of the journal.
Results of this study, based on blood samples from nearly 650 SARS-CoV-2 infected individuals in Switzerland, Italy and the United States, demonstrate that the magnitude of antibodies produced by an infected individual is proportional to disease severity (with hospitalized patients possessing higher antibody titers compared to non-hospitalized patients), and that those antibodies have a half-life of less than two months. Scientists also report that the receptor binding domain (RBD) of the virus is the main target of naturally occurring neutralizing antibodies, accounting for 90% of the neutralizing activity in serum.
“This study provides new information about the diverse individual antibody response to SARS-CoV-2 infection. The results establish a blueprint that could help guide future serology studies and inform vaccine and therapeutic design strategies,” said Davide Corti, senior vice president of antibody research at Vir and study author. “Further, the rapid waning of the natural antibody response and the fact that approximately 60% of infected individuals do not produce antibodies that can block infection underscores the potential need for additional therapeutic approaches.”
The manuscript also describes the structural characteristics of the interactions of six different neutralizing antibodies targeting the SARS-CoV-2 RBD, including S309. As described in the July 9, 2020 print edition of Nature, S309 was isolated from a patient who recovered from severe acute respiratory syndrome (SARS) in 2003, and has been shown to be effective against SARS-CoV-2 infection in cells and in animal models. The findings published in Cell demonstrate that S309 has a high affinity for binding to a different part of the RBD compared to the other five monoclonal antibodies examined, and one that Vir believes may be less likely to mutate. S309 also promotes effector function, enhancing its ability to kill infected cells in addition to its potent neutralizing effect.
“Our high-resolution look at the binding characteristics of the six antibodies highlights nuanced differences that correlate with specific functional activity,” said David Veesler, Ph.D., Associate Professor of Biochemistry at the University of Washington School of Medicine and study author. “This unique approach to analyzing antibody responses in infected individuals could be key to ensuring optimal characteristics in the design of future COVID-19 vaccines and therapeutics.”
Vir, in collaboration with GlaxoSmithKline plc, is advancing COVID-19 monoclonal antibodies based on the S309 antibody, including VIR-7831 (also known as GSK4182136) and VIR-7832. In August, the companies initiated a Phase 2/3 study, called COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial - Intent to Care Early), which is evaluating VIR-7831 for the early treatment of COVID-19 in patients at high risk of hospitalization.
The research published in Cell was conducted by Vir’s subsidiary Humabs BioMed SA in collaboration with the Institute for Research in Biomedicine (IRB), which is affiliated with the Università della Svizzera italiana in Bellinzona, Switzerland; the Ente Ospedaliero Cantonale (EOC) in Ticino, Switzerland; the Clinica Luganese Moncucco in Lugano, Switzerland; the Università della Svizzera italiana (USI); the Luigi Sacco University Hospital in Milan; and the University of Washington in Seattle.
Key contributors include Dr. Veesler; Paolo Ferrari, M.D., chief medical officer for EOC; Federica Sallusto, professor at ETH Zurich and director of the Center of Medical Immunology at the IRB affiliated with the Università della Svizzera italiana; Christian Garzoni, M.D., specialist in general internal medicine and infectious diseases for Clinica Luganese Moncucco; and Agostino Riva, M.D., attending physician at the Luigi Sacco University Hospital.
“We wish to thank our many collaborators and partners who dedicated substantial resources and attention to ensuring the collection, screening and preparation of thousands of samples in just a few weeks,” said Herbert “Skip” Virgin, M.D., Ph.D., chief scientific officer of Vir. “Their efforts were important to advancing our understanding of how to combat this global health crisis. We are grateful for their collective focus and collaboration on this research, which represents a key step in the fight against COVID-19.”