A trio of papers describes several newly discovered human antibodies that target the SARS-CoV-2 virus, isolated from survivors of SARS-CoV-2 and SARS-CoV infection. Several of these antibodies showed protective, neutralizing capabilities, offering promising therapeutic leads, and eight antibodies from one analysis were discovered to cross-react with a related bat-specific coronavirus - with implications for the identification of broadly neutralizing antibodies to protect against potential new coronavirus outbreaks in the future.
Philip Brouwer and colleagues isolated 403 monoclonal antibodies from 3 convalescent COVID-19 patients, showing that the patients had strong immune responses against the viral spike, a protein complex that binds to the ACE2 receptor to facilitate entry into human host cells. A subset of these antibodies neutralized the virus by targeting diverse epitopes on the spike, with the two most potent ones targeting the domain that binds the host receptor. In another study, Thomas Rogers and colleagues used a high-throughput pipeline to isolate and characterize monoclonal antibodies from convalescent donors, selecting for antibodies that bind to the viral spike.
Several of the isolated antibodies bound to the receptor binding domain (RBD) and demonstrated neutralizing capabilities, with the most potent ones binding at a site that overlaps the ACE2 binding site. Two of these neutralizing antibodies gave protection against SARS-CoV-2 infection when tested in Syrian hamsters. In a third study to identify broadly protective, cross-reactive antibodies, Anna Wec and colleagues isolated and characterized hundreds of antibodies against the viral spike of SARS-CoV-2 from the memory B cells of a SARS-CoV survivor. Both of these closely related viruses rely on the spike to gain host cell entry by binding the ACE2 receptor. Of nine antibodies that showed strong cross-neutralization of both viruses, eight target the domain that binds the ACE2 receptor - and also neutralized a closely related species of bat coronavirus.
Taken together, the trio of studies offers several new human antibodies to help inform the design of therapeutic antibody drugs and vaccines against SARS-CoV-2, as well as the design of broadly protective vaccines against a range of related coronaviruses.
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Journal reference:
Brouwer, P.J.M., et al. (2020) Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science. doi.org/10.1126/science.abc5902.