A team of researchers from Stanford University has developed a promising method to counteract the constantly mutating virus responsible for COVID-19. The study, published in Science Translational Medicine, highlights a novel approach using bispecific antibodies that could potentially offer longer-lasting treatments.
The research team discovered that pairing two antibodies can effectively neutralize the virus. One antibody serves as an anchor by attaching to a stable region of the virus, while the other prevents the virus from infecting cells. This method was shown to be effective against both the original SARS-CoV-2 virus and all its variants up to omicron during laboratory tests.
“In the face of an ever-changing virus, we engineered a new generation of therapeutics that have the ability to be resistant to viral evolution, which could be useful many years down the road for the treatment of people infected with SARS-CoV-2,” stated Christopher O. Barnes, assistant professor of biology at Stanford and senior author of the study.
The investigation led by Barnes and first author Adonis Rubio involved analyzing antibodies from recovered COVID-19 patients. They identified one antibody that attaches to a rarely mutating area within the Spike N-terminal domain (NTD) of the virus. This discovery is crucial for designing therapies that allow another antibody to block the receptor-binding domain (RBD), thereby preventing viral infection in human cells.
The bispecific antibodies, named CoV2-biRN, demonstrated high neutralization efficacy against known variants in laboratory settings and significantly reduced viral load in mice lungs exposed to an omicron variant.
Further research and clinical trials are necessary before this discovery can be applied as a treatment for humans. However, researchers see potential beyond COVID-19, aiming to design bispecific antibodies effective against all coronaviruses and possibly influenza and HIV.
“Viruses constantly evolve to maintain the ability to infect the population,” Barnes noted. “To counter this, the antibodies we develop must continuously evolve as well to remain effective.”
The research includes contributions from Stanford undergraduates Megan Parada; biology staff scientist Morgan Abernathy; life science researcher Yu E. Lee; biology lab technician Michael Eso; biophysics doctoral student Gina El Nesr; and former lab technicians Israel Ramos, Teresia Chen, and Jennie Phung. Co-authors also include members from Rockefeller University, Fred Hutchinson Cancer Center in Seattle, and Howard Hughes Medical Institute.
This work received support from various institutions including Chan Zuckerberg Biohub, National Institutes of Health, National Science Foundation, Pew Biomedical Scholars Program, and Rita Allen Foundation.
Rockefeller University has filed a provisional patent application related to monoclonal antibodies described in this work with co-authors Zijun Wang and Michel C. Nussenzweig listed as inventors (U.S. patent 17/575,246). Jesse D. Bloom from Fred Hutchinson Cancer Center consults for several companies including Moderna while Bernadeta Dadonaite also consults for Moderna.
Media contact: Sara Zaske at Stanford School of Humanities and Sciences can be reached at szaske@stanford.edu.
