Details

Autor(en) / Beteiligte

• Zhou, Panpan
• Yuan, Meng
• Song, Ge
• Beutler, Nathan
• Shaabani, Namir
• Huang, Deli
• He, Wan-Ting
• Zhu, Xueyong
• Callaghan, Sean
• Yong, Peter
• Anzanello, Fabio
• Peng, Linghang
• Ricketts, James
• Parren, Mara
• Garcia, Elijah
• Rawlings, Stephen A
• Smith, Davey M
• Nemazee, David
• Teijaro, John R
• Rogers, Thomas F
• Wilson, Ian A
• Burton, Dennis R
• Andrabi, Raiees

Titel

A human antibody reveals a conserved site on beta-coronavirus spike proteins and confers protection against SARS-CoV-2 infection

Ist Teil von

• Science translational medicine, 2022-03, Vol.14 (637), p.eabi9215

Ort / Verlag

United States

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• Broadly neutralizing antibodies (bnAbs) to coronaviruses (CoVs) are valuable in their own right as prophylactic and therapeutic reagents to treat diverse CoVs and as templates for rational pan-CoV vaccine design. We recently described a bnAb, CC40.8, from a CoV disease 2019 (COVID-19) convalescent donor that exhibits broad reactivity with human β-CoVs. Here, we showed that CC40.8 targets the conserved S2 stem helix region of the CoV 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 that 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.