Broad neutralization of SARS-related viruses by human monoclonal antibodies.
Anna Z WecDaniel WrappAndrew S HerbertDaniel P MaurerDenise HaslwanterMrunal SakharkarRohit K JangraMaria Eugenia DieterleAsparouh LilovDeli HuangLongping V TseNicole V JohnsonChing-Lin HsiehNianshuang WangJuergen H NettElizabeth ChampneyIrina BurninaMichael E BrownShu LinMelanie SinclairCarl JohnsonSarat PudiRobert H BortzAriel S WirchnianskiEthan LaudermilchCatalina FlorezJ Maximilian FelsCecilia M O'BrienBarney S GrahamDavid NemazeeDennis R BurtonRalph S BaricJames E VossKartik ChandranJohn M DyeJason S MclellanLaura M WalkerPublished in: Science (New York, N.Y.) (2020)
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.