Seeking broad protection As scientists develop therapeutic antibodies and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the risk of emergent coronaviruses makes it important to also identify broadly protective antibodies. Wec et al. isolated and characterized hundreds of antibodies against the viral spike protein of SARS-CoV-2 from the memory B cells of a survivor of the 2003 outbreak caused by the related coronavirus, SARS-CoV. In both of these viruses, the spike protein facilitated viral entry by binding to the angiotensin-converting enzyme 2 (ACE2) receptor on human cells. The antibodies targeted multiple sites on the spike protein, but of nine antibodies that showed strong cross-neutralization, eight targeted the domain that binds to ACE2. These eight antibodies also neutralized a bat SARS-related virus. Illuminating the epitopes on the viral spike protein that bind cross-neutralizing antibodies could guide the design of broadly protective vaccines. Science , this issue p. 731 Broadly neutralizing antibodies that target overlapping epitopes on the SARS-CoV-2 spike protein have been isolated. Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 200 SARS coronavirus 2 (SARS-CoV-2) binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of preexisting memory B cells elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines.
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