학술논문
Targeted isolation of diverse human protective broadly neutralizing antibodies against SARS-like viruses
Document Type
article
Author
He, Wan-ting; Musharrafieh, Rami; Song, Ge; Dueker, Katharina; Tse, Longping V; Martinez, David R; Schäfer, Alexandra; Callaghan, Sean; Yong, Peter; Beutler, Nathan; Torres, Jonathan L; Volk, Reid M; Zhou, Panpan; Yuan, Meng; Liu, Hejun; Anzanello, Fabio; Capozzola, Tazio; Parren, Mara; Garcia, Elijah; Rawlings, Stephen A; Smith, Davey M; Wilson, Ian A; Safonova, Yana; Ward, Andrew B; Rogers, Thomas F; Baric, Ralph S; Gralinski, Lisa E; Burton, Dennis R; Andrabi, Raiees
Source
Nature Immunology. 23(6)
Subject
Language
Abstract
The emergence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) and potential future spillovers of SARS-like coronaviruses into humans pose a major threat to human health and the global economy. Development of broadly effective coronavirus vaccines that can mitigate these threats is needed. Here, we utilized a targeted donor selection strategy to isolate a large panel of human broadly neutralizing antibodies (bnAbs) to sarbecoviruses. Many of these bnAbs are remarkably effective in neutralizing a diversity of sarbecoviruses and against most SARS-CoV-2 VOCs, including the Omicron variant. Neutralization breadth is achieved by bnAb binding to epitopes on a relatively conserved face of the receptor-binding domain (RBD). Consistent with targeting of conserved sites, select RBD bnAbs exhibited protective efficacy against diverse SARS-like coronaviruses in a prophylaxis challenge model in vivo. These bnAbs provide new opportunities and choices for next-generation antibody prophylactic and therapeutic applications and provide a molecular basis for effective design of pan-sarbecovirus vaccines.