Anna Z. Wec, D. Wrapp, A. Herbert, Daniel P Maurer, D. Haslwanter, M. Sakharkar, R. Jangra, M. Dieterle, A. Lilov, Deli Huang, L. V. Tse, Nicole V. Johnson, C. Hsieh, N. Wang, J. Nett, E. Champney, Irina Burnina, Michael E Brown, Shu Lin, M. Sinclair, Carl Johnson, Sarat Pudi, R. Bortz, A. S. Wirchnianski, E. Laudermilch, C. Florez, J. Fels, C. M. O’Brien, B. Graham, D. Nemazee, D. Burton, R. Baric, J. Voss, K. Chandran, J. Dye, J. McLellan, L. Walker
Science, 2020
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.
Cited by 241 publications.
Field of study: Medicine