Journal: Nat Immunol / Year: 2022 Title: Targeted isolation of diverse human protective broadly neutralizing antibodies against SARS-like viruses. Authors: Wan-Ting He / Rami Musharrafieh / Ge Song / Katharina Dueker / Longping V Tse / David R Martinez / Alexandra Schäfer / Sean Callaghan / Peter Yong / Nathan Beutler / Jonathan L Torres / ...Authors: Wan-Ting He / Rami Musharrafieh / Ge Song / Katharina Dueker / Longping V Tse / David R Martinez / Alexandra Schäfer / Sean Callaghan / Peter Yong / Nathan Beutler / Jonathan L Torres / Reid M Volk / Panpan Zhou / Meng Yuan / Hejun Liu / Fabio Anzanello / Tazio Capozzola / Mara Parren / Elijah Garcia / Stephen A Rawlings / Davey M Smith / Ian A Wilson / Yana Safonova / Andrew B Ward / Thomas F Rogers / Ralph S Baric / Lisa E Gralinski / Dennis R Burton / Raiees Andrabi / 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 ...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.
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