EMD-26525
SARS-CoV-2 6P Mut7 in complex with K398.16 Fab (3 bound)
EMD-26525
Single-particle25.0 Å
Deposition: 28/03/2022
Map released: 08/06/2022
Last modified: 17/01/2024
Sample Organism:
Severe acute respiratory syndrome coronavirus 2,
Macaca mulatta
Sample: SARS-CoV-2 6P Mut7 in complex with K398.16 Fab (3 bound)
Deposition Authors: Lee WH , Torres JL , Ward AB
Sample: SARS-CoV-2 6P Mut7 in complex with K398.16 Fab (3 bound)
Deposition Authors: Lee WH , Torres JL , Ward AB
Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques.
He WT ,
Yuan M ,
Callaghan S ,
Musharrafieh R ,
Song G ,
Silva M ,
Beutler N ,
Lee WH ,
Yong P ,
Torres JL ,
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 SA ,
Nemazee D ,
Smith DM ,
Briney B ,
Safonova Y ,
Rogers TF ,
Dan JM ,
Zhang Z,
Weiskopf D ,
Sette A ,
Crotty S ,
Irvine DJ ,
Ward AB ,
Wilson IA ,
Burton DR ,
Andrabi R
(2022) Sci Transl Med , 14 , eabl9605 - eabl9605
(2022) Sci Transl Med , 14 , eabl9605 - eabl9605
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.
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.