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October 19, 2021
Understanding SARS-CoV-2 antibody binding
At a Glance
- Researchers mapped where various antibodies bind to the SARS-CoV-2 spike protein.
- The results could help in designing more effective antibody therapies for COVID-19.
The body’s defense against SARS-CoV-2 relies on antibodies against the viral spike protein. But many mutations have arisen in the SARS-CoV-2 spike protein since the virus first emerged. Such mutations could allow the virus to evade antibody-based defenses. Scientists would like to develop improved antibody therapies that the virus cannot evade through mutation. Doing so requires a detailed understanding of how various antibodies bind to the spike protein. Such an understanding could also help in predicting how new mutations may affect treatment.
To build this level of understanding, researchers led by Dr. Erica Ollmann Saphire at the La Jolla Institute for Immunology established the Coronavirus Immunotherapeutic Consortium (CoVIC). NIH’s National Institute for Allergy and Infectious Diseases (NIAID) provided funding.
CoVIC now includes 370 antibodies against the spike protein that were contributed by more than 50 partners around the world. The consortium analyzes these antibodies in a standardized fashion. Results of the study were published in Science on September 23, 2021.
Most of the antibodies examined target the receptor-binding domain (RBD) of the spike protein. When binding to the spike protein, certain pairs of antibodies competed with each other, while others did not. This suggests that the competing antibodies were binding to the same part of the spike protein. Based on these competition patterns, the researchers grouped the antibodies into seven “communities.” Using electron microscopy, they determined each community’s “footprint”— where it binds on the surface. This analysis confirmed that each community of antibodies recognized a distinct part of the RBD.
The researchers also measured how well antibodies were able to neutralize viruses carrying various spike mutations. The effects of mutations depended in part on which community antibodies belonged to. Many mutations occur where the spike protein contacts its host cell receptor. These mutations could inhibit neutralization by antibodies whose footprints overlapped this area. But three communities had footprints elsewhere on the spike. These communities could neutralize the virus effectively regardless of which mutations were present.
“We were able to map the geography of Spike and understand which antibodies bind to which footprints,” Saphire says. “This map provides a reference to help predict which antibodies are still effective against SARS-CoV-2 variants of concern like the currently surging Delta variant.”
The results also provide a framework for identifying the most effective antibody cocktail. A cocktail of antibodies from many communities would likely be more effective than one from any single community. Antibodies from the mutation-resistant communities could be vital components of such a cocktail.
“If you are making an antibody cocktail, you’d want at least one of those antibodies in there because they are probably going to maintain their efficacy against most variants,” says co-first author Dr. Kathryn Hastie.
“The CoVIC contributors used different strategies to find these antibodies,” explains co-first author Dr. Haoyang Li. “This breadth of antibodies makes our study more comprehensive than previous studies that might have looked at antibodies from a small pool of survivors.”
—by Brian Doctrow, Ph.D.
- How COVID-19 Variants Evade Immune Response
- Potent Neutralizing Antibodies Target New Regions of Coronavirus Spike
- Potent Antibodies Found in People Recovered From COVID-19
- Novel Coronavirus Structure Reveals Targets for Vaccines and Treatments
- Developing Therapeutics and Vaccines for Coronaviruses
- COVID-19 Research
- COVID-19 (CDC)
References: Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study. Hastie KM, Li H, Bedinger D, Schendel SL, Dennison SM, Li K, Rayaprolu V, Yu X, Mann C, Zandonatti M, Diaz Avalos R, Zyla D, Buck T, Hui S, Shaffer K, Hariharan C, Yin J, Olmedillas E, Enriquez A, Parekh D, Abraha M, Feeney E, Horn GQ; CoVIC-DB team1, Aldon Y, Ali H, Aracic S, Cobb RR, Federman RS, Fernandez JM, Glanville J, Green R, Grigoryan G, Lujan Hernandez AG, Ho DD, Huang KA, Ingraham J, Jiang W, Kellam P, Kim C, Kim M, Kim HM, Kong C, Krebs SJ, Lan F, Lang G, Lee S, Leung CL, Liu J, Lu Y, MacCamy A, McGuire AT, Palser AL, Rabbitts TH, Rikhtegaran Tehrani Z, Sajadi MM, Sanders RW, Sato AK, Schweizer L, Seo J, Shen B, Snitselaar JJ, Stamatatos L, Tan Y, Tomic MT, van Gils MJ, Youssef S, Yu J, Yuan TZ, Zhang Q, Peters B, Tomaras GD, Germann T, Saphire EO. Science. 2021 Sep 23:eabh2315. doi: 10.1126/science.abh2315. Online ahead of print. PMID: 34554826.
Funding: NIH’s National Institute of Allergy and Infectious Diseases (NIAID); Overton family; COVID-19 Therapeutics Accelerator; Bill and Melinda Gates Foundation; GHR Foundation; Carolee Lee; The Mercatus Center at George Mason University; Swiss National Science Foundation; Translating Duke Health Immunology Initiative