7TP4

Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibody K398.22

Summary for 7TP4

• Entry DOI: 10.2210/pdb7tp4/pdb
• Descriptor: Spike protein S1, K398.22 heavy chain, K398.22 light chain, ... (6 entities in total)
• Functional Keywords: sars-cov-2, antibody, neutralizing antibody, fab, covid-19, coronavirus, receptor-binding domain, rbd, immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 3
• Total formula weight: 70418.44

Authors

Yuan, M.,Zhu, X.,Wilson, I.A. (deposition date: 2022-01-24, release date: 2022-02-23, Last modification date: 2024-11-13)

Primary citation

He, W.T.,Yuan, M.,Callaghan, S.,Musharrafieh, R.,Song, G.,Silva, M.,Beutler, N.,Lee, W.H.,Yong, P.,Torres, J.L.,Melo, M.,Zhou, P.,Zhao, F.,Zhu, X.,Peng, L.,Huang, D.,Anzanello, F.,Ricketts, J.,Parren, M.,Garcia, E.,Ferguson, M.,Rinaldi, W.,Rawlings, S.A.,Nemazee, D.,Smith, D.M.,Briney, B.,Safonova, Y.,Rogers, T.F.,Dan, J.M.,Zhang, Z.,Weiskopf, D.,Sette, A.,Crotty, S.,Irvine, D.J.,Ward, A.B.,Wilson, I.A.,Burton, D.R.,Andrabi, R.
Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques.
Sci Transl Med, 14:eabl9605-eabl9605, 2022

PubMed Abstract: To prepare for future coronavirus (CoV) pandemics, it is desirable to generate vaccines capable of eliciting broadly neutralizing antibody responses to CoVs. Here, we show that immunization of macaques with SARS-CoV-2 spike (S) protein with a two-shot protocol generated potent serum receptor binding domain cross-neutralizing antibody responses to both SARS-CoV-2 and SARS-CoV-1. Furthermore, responses were equally effective against most SARS-CoV-2 variants of concern (VOCs) and some were highly effective against Omicron. This result contrasts with human infection or many two-shot vaccination protocols where responses were typically more SARS-CoV-2 specific and where VOCs were less well neutralized. Structural studies showed that cloned macaque neutralizing antibodies, particularly using a given heavy chain germline gene, recognized a relatively conserved region proximal to the angiotensin converting enzyme 2 receptor binding site (RBS), whereas many frequently elicited human neutralizing antibodies targeted more variable epitopes overlapping the RBS. B cell repertoire differences between humans and macaques appeared to influence the vaccine response. The macaque neutralizing antibodies identified a pan-SARS-related virus epitope region less well targeted by human antibodies that could be exploited in rational vaccine design.

PubMed: 35947674
DOI: 10.1126/scitranslmed.abl9605

Experimental method

X-RAY DIFFRACTION (1.95 Å)