tetano
Editor, Senior Moderator
Nat Immunol
. 2022 Jun 2.
doi: 10.1038/s41590-022-01222-1. Online ahead of print.
Targeted isolation of diverse human protective broadly neutralizing antibodies against SARS-like viruses
Wan-Ting He[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Rami Musharrafieh[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Ge Song[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Katharina Dueker[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Longping V Tse[SUP] 4 [/SUP], David R Martinez[SUP] 4 [/SUP], Alexandra Schäfer[SUP] 4 [/SUP], Sean Callaghan[SUP] 1 2 3 [/SUP], Peter Yong[SUP] 1 2 3 [/SUP], Nathan Beutler[SUP] 1 [/SUP], Jonathan L Torres[SUP] 5 [/SUP], Reid M Volk[SUP] 5 [/SUP], Panpan Zhou[SUP] 1 2 3 [/SUP], Meng Yuan[SUP] 5 [/SUP], Hejun Liu[SUP] 5 [/SUP], Fabio Anzanello[SUP] 1 2 3 [/SUP], Tazio Capozzola[SUP] 1 2 3 [/SUP], Mara Parren[SUP] 1 [/SUP], Elijah Garcia[SUP] 1 [/SUP], Stephen A Rawlings[SUP] 6 [/SUP], Davey M Smith[SUP] 6 [/SUP], Ian A Wilson[SUP] 2 3 5 7 [/SUP], Yana Safonova[SUP] 8 [/SUP], Andrew B Ward[SUP] 2 3 5 [/SUP], Thomas F Rogers[SUP] 1 6 [/SUP], Ralph S Baric[SUP] 9 10 [/SUP], Lisa E Gralinski[SUP] 11 [/SUP], Dennis R Burton[SUP] 12 13 14 15 [/SUP], Raiees Andrabi[SUP] 16 17 18 [/SUP]
Affiliations
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.
. 2022 Jun 2.
doi: 10.1038/s41590-022-01222-1. Online ahead of print.
Targeted isolation of diverse human protective broadly neutralizing antibodies against SARS-like viruses
Wan-Ting He[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Rami Musharrafieh[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Ge Song[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Katharina Dueker[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Longping V Tse[SUP] 4 [/SUP], David R Martinez[SUP] 4 [/SUP], Alexandra Schäfer[SUP] 4 [/SUP], Sean Callaghan[SUP] 1 2 3 [/SUP], Peter Yong[SUP] 1 2 3 [/SUP], Nathan Beutler[SUP] 1 [/SUP], Jonathan L Torres[SUP] 5 [/SUP], Reid M Volk[SUP] 5 [/SUP], Panpan Zhou[SUP] 1 2 3 [/SUP], Meng Yuan[SUP] 5 [/SUP], Hejun Liu[SUP] 5 [/SUP], Fabio Anzanello[SUP] 1 2 3 [/SUP], Tazio Capozzola[SUP] 1 2 3 [/SUP], Mara Parren[SUP] 1 [/SUP], Elijah Garcia[SUP] 1 [/SUP], Stephen A Rawlings[SUP] 6 [/SUP], Davey M Smith[SUP] 6 [/SUP], Ian A Wilson[SUP] 2 3 5 7 [/SUP], Yana Safonova[SUP] 8 [/SUP], Andrew B Ward[SUP] 2 3 5 [/SUP], Thomas F Rogers[SUP] 1 6 [/SUP], Ralph S Baric[SUP] 9 10 [/SUP], Lisa E Gralinski[SUP] 11 [/SUP], Dennis R Burton[SUP] 12 13 14 15 [/SUP], Raiees Andrabi[SUP] 16 17 18 [/SUP]
Affiliations
- PMID: 35654851
- DOI: 10.1038/s41590-022-01222-1
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.