Scientists at La Jolla Institute for Immunology (LJI) have published a detailed map of where human antibodies bind to SARS-CoV-2, a map that was generated by a global collaboration comparing nearly all leading clinical candidates. The new research, published in Science, will help guide the development of more effective COVID-19 antibody therapies and help scientists develop effective vaccines to address emerging viral variants. The findings propel COVID-19 research in three key ways:
- Hundreds of antibodies contributed by over 50 different organizations around the world were classified and mapped. This study shows exactly where each antibody binds on the Spike protein of SARS-CoV-2.
- The researchers describe the neutralizing strength, or potency, of each antibody and the likelihood that each antibody could offer protection against viral variants.
- Antibodies with similar footprints on Spike were grouped into “communities.” The researchers show how antibodies from different communities could be combined in a powerful antibody “cocktail” to target the virus.
“We were able to map the geography of Spike and understand which antibodies bind to which footprints. 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,” says LJI Professor Erica Ollmann Saphire, Ph.D., who leads the global effort behind this research, called the Coronavirus Immunotherapeutic Consortium (CoVIC). In fact, the researchers found three different groups of antibodies that are resistant to mutations in SARS-CoV-2 Spike protein. These antibodies could target vulnerable sites on the Spike protein, even as it mutates. “We now have a framework for selecting durable antibody cocktails for COVID-19 treatment,” says Saphire. Adds study co-first author Kathryn Hastie, Ph.D., an instructor at LJI: “CoVIC was formed to analyse a huge panel of monoclonal antibodies on equal footing. The initial goal was to look at antibodies against the original SARS-CoV-2 strain, but it quickly became clear that the virus’s Spike protein was ever-evolving. The ability of the Spike to change has serious implications when you are talking about treating someone with a monoclonal antibody.”