Summary: S309, a neutralizing antibody first identified in blood samples from a patient who recovered from SARS in 2003, shows promise for the treatment of COVID-19.
Source: University of Washington
An antibody first identified in a blood sample from a patient who recovered from Severe Acute Respiratory Syndrome in 2003 inhibits related coronaviruses, including the cause of COVID-19. The antibody, called S309, is now on a fast-track development and testing path at Vir Biotechnology in the next step toward possible clinical trials.
Laboratory research findings on the S309 antibody are reported in the May 18 edition of Nature. The title of the paper, available here, is: “Cross-neutralization of SARS-CoV and SARS-CoV2 by a human monoclonal antibody.”
The senior authors on the paper are David Veesler, assistant professor of biochemistry at the University of Washington School of Medicine, and Davide Corti of Humabs Biomed SA, a subsidiary of Vir. The lead authors are Dora Pinto and Martina Beltramello of Humabs, as well as Young-Jun Park and Lexi Walls, research scientists in the Veesler lab, which for several years has been studying the structure and function of the infection mechanisms on a variety of coronaviruses
“We still need to show that this antibody is protective in living systems, which has not yet been done,” Veesler said.
“Right now there are no approved tools or licensed therapeutics proven to fight against the coronavirus that causes COVID-19,” he added. If the antibody is shown to work against the novel coronavirus in people, it could become part of the pandemic armamentarium.
Veesler said that his lab is not the only one seeking neutralizing antibodies for COVID 19 treatment. What makes this antibody different is that its search did not take place in people who had COVID-19, but in someone who had been infected 17 years ago during a SARS epidemic.
“This is what allowed us to move so fast compared to other groups,” Veesler said.
The scientists identified several monoclonal antibodies of interest from memory B cells of the SARS survivor. Memory B cells form following an infectious illness. Their lineage can last, sometimes for life. They usually remember a pathogen, or one similar to it, that the body has ousted in the past, and launch an antibody defense against a re-infection.
Several of the antibodies from the SARS survivor’s memory B cells are directed at a protein structure on coronaviruses. This structure is critical to the coronaviruses’ ability to recognize a receptor on a cell, fuse to it, and inject their genetic material into the cell. This infectivity machinery is located in the spikes that crown the coronavirus.
The S309 antibody is particularly potent at targeting and disabling the spike protein that promotes the coronavirus entry into cells. It was able to neutralize SARS CoV-2 by engaging with a section of the spike protein nearby the attachment site to the host cell.
Through their cryo-electronmicroscopy studies and binding assays, the researchers learned that the S309 antibody recognizes a binding site on the coronavirus that is conserved across many sarbocoviruses, not just the SARS and COVID-19 viruses. That is probably why this antibody, instead of being single-minded, is able to act against related coronaviruses.
Credit: UW Medicine.
Combining the S309 antibody with other, though weaker, antibodies identified in the recovered SARS patient enhanced the neutralization of the COVID-19 coronavirus.
This multiple antibody cocktail approach might help limit the coronavirus’ ability to form mutants capable of escaping a single-ingredient antibody treatment, according to the researchers.
The scientists noted that they hope these initial results pave the way for using the S309 antibody, alone or in a mixture, as a preventive measure for people at high-risk of exposure to the COVID-19 coronavirus or as post-exposure therapy to limit or treat severe illness.
Other research institutions participating in this research include Institut Pasteur in France, the Università della Svizzera Italiana in Switzerland, and Washington University in St. Louis, Missouri.
Funding: This study was supported by the National Institute of General Medical Sciences {R01GM120553), National Institute of Allergy and Infectious Diseases (HHSN272201700059C), Pew Biomedical Scholars Award, Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund, University of Washington Arnold and Mabel Beckman cryoEM Center, the Pasteur Institute, and the beamline at the Advanced Light Source at Lawrence Berkley National Laboratory. The researchers obtained viral genomic sequences from GISAID’s EpiFlu Database, hosted by the German government.
About this coronavirus research article
Source:
University of Washington
Media Contacts:
Leila Gray – University of Washington
Image Source:
The image is in the public domain.
Original Research: Closed access
“Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody”. by Dora Pinto, Young-Jun Park, Martina Beltramello, Alexandra C. Walls, M. Alejandra Tortorici, Siro Bianchi, Stefano Jaconi, Katja Culap, Fabrizia Zatta, Anna De Marco, Alessia Peter, Barbara Guarino, Roberto Spreafico, Elisabetta Cameroni, James Brett Case, Rita E. Chen, Colin Havenar-Daughton, Gyorgy Snell, Amalio Telenti, Herbert W. Virgin, Antonio Lanzavecchia, Michael S. Diamond, Katja Fink, David Veesler & Davide Corti.
Naure doi:10.1038/s41586-020-2349-y
Abstract
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody
SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 20201,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of an individual who was infected with SARS-CoV in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309- and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease.
Feel Free To Share This COVID-19 News.