tetano
Editor, Senior Moderator
Sci Transl Med
. 2022 Feb 8;eabi9215.
doi: 10.1126/scitranslmed.abi9215. Online ahead of print.
A human antibody reveals a conserved site on beta-coronavirus spike proteins and confers protection against SARS-CoV-2 infection
Panpan Zhou[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Meng Yuan[SUP] #[/SUP][SUP] 4 [/SUP], Ge Song[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Nathan Beutler[SUP] #[/SUP][SUP] 1 [/SUP], Namir Shaabani[SUP] #[/SUP][SUP] 1 [/SUP], Deli Huang[SUP] 1 [/SUP], Wan-Ting He[SUP] 1 2 3 [/SUP], Xueyong Zhu[SUP] 4 [/SUP], Sean Callaghan[SUP] 1 2 3 [/SUP], Peter Yong[SUP] 1 2 3 [/SUP], Fabio Anzanello[SUP] 1 2 3 [/SUP], Linghang Peng[SUP] 1 [/SUP], James Ricketts[SUP] 1 [/SUP], Mara Parren[SUP] 1 [/SUP], Elijah Garcia[SUP] 1 [/SUP], Stephen A Rawlings[SUP] 5 [/SUP], Davey M Smith[SUP] 5 [/SUP], David Nemazee[SUP] 1 [/SUP], John R Teijaro[SUP] 1 [/SUP], Thomas F Rogers[SUP] 1 5 [/SUP], Ian A Wilson[SUP] 4 2 3 6 [/SUP], Dennis R Burton[SUP] 1 2 3 7 [/SUP], Raiees Andrabi[SUP] 1 2 3 [/SUP]
Affiliations
Abstract
Broadly neutralizing antibodies (bnAbs) to coronaviruses (CoVs) are valuable in their own right as prophylactic and therapeutic reagents to treat diverse CoVs and, importantly, as templates for rational pan-CoV vaccine design. We recently described a bnAb, CC40.8, from a coronavirus disease 2019 (COVID-19)-convalescent donor that exhibits broad reactivity with human beta-coronaviruses (β-CoVs). Here, we showed that CC40.8 targets the conserved S2 stem-helix region of the coronavirus spike fusion machinery. We determined a crystal structure of CC40.8 Fab with a SARS-CoV-2 S2 stem-peptide at 1.6 Å resolution and found that the peptide adopted a mainly helical structure. Conserved residues in β-CoVs interacted with CC40.8 antibody, thereby providing a molecular basis for its broad reactivity. CC40.8 exhibited in vivo protective efficacy against SARS-CoV-2 challenge in two animal models. In both models, CC40.8-treated animals exhibited less weight loss and reduced lung viral titers compared to controls. Furthermore, we noted CC40.8-like bnAbs are relatively rare in human COVID-19 infection and therefore their elicitation may require rational structure-based vaccine design strategies. Overall, our study describes a target on β-CoV spike proteins for protective antibodies that may facilitate the development of pan-β-CoV vaccines.
. 2022 Feb 8;eabi9215.
doi: 10.1126/scitranslmed.abi9215. Online ahead of print.
A human antibody reveals a conserved site on beta-coronavirus spike proteins and confers protection against SARS-CoV-2 infection
Panpan Zhou[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Meng Yuan[SUP] #[/SUP][SUP] 4 [/SUP], Ge Song[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Nathan Beutler[SUP] #[/SUP][SUP] 1 [/SUP], Namir Shaabani[SUP] #[/SUP][SUP] 1 [/SUP], Deli Huang[SUP] 1 [/SUP], Wan-Ting He[SUP] 1 2 3 [/SUP], Xueyong Zhu[SUP] 4 [/SUP], Sean Callaghan[SUP] 1 2 3 [/SUP], Peter Yong[SUP] 1 2 3 [/SUP], Fabio Anzanello[SUP] 1 2 3 [/SUP], Linghang Peng[SUP] 1 [/SUP], James Ricketts[SUP] 1 [/SUP], Mara Parren[SUP] 1 [/SUP], Elijah Garcia[SUP] 1 [/SUP], Stephen A Rawlings[SUP] 5 [/SUP], Davey M Smith[SUP] 5 [/SUP], David Nemazee[SUP] 1 [/SUP], John R Teijaro[SUP] 1 [/SUP], Thomas F Rogers[SUP] 1 5 [/SUP], Ian A Wilson[SUP] 4 2 3 6 [/SUP], Dennis R Burton[SUP] 1 2 3 7 [/SUP], Raiees Andrabi[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 35133175
- DOI: 10.1126/scitranslmed.abi9215
Abstract
Broadly neutralizing antibodies (bnAbs) to coronaviruses (CoVs) are valuable in their own right as prophylactic and therapeutic reagents to treat diverse CoVs and, importantly, as templates for rational pan-CoV vaccine design. We recently described a bnAb, CC40.8, from a coronavirus disease 2019 (COVID-19)-convalescent donor that exhibits broad reactivity with human beta-coronaviruses (β-CoVs). Here, we showed that CC40.8 targets the conserved S2 stem-helix region of the coronavirus spike fusion machinery. We determined a crystal structure of CC40.8 Fab with a SARS-CoV-2 S2 stem-peptide at 1.6 Å resolution and found that the peptide adopted a mainly helical structure. Conserved residues in β-CoVs interacted with CC40.8 antibody, thereby providing a molecular basis for its broad reactivity. CC40.8 exhibited in vivo protective efficacy against SARS-CoV-2 challenge in two animal models. In both models, CC40.8-treated animals exhibited less weight loss and reduced lung viral titers compared to controls. Furthermore, we noted CC40.8-like bnAbs are relatively rare in human COVID-19 infection and therefore their elicitation may require rational structure-based vaccine design strategies. Overall, our study describes a target on β-CoV spike proteins for protective antibodies that may facilitate the development of pan-β-CoV vaccines.