EMD-21961
Cryo-EM structure of the VRC315 clinical trial, vaccine-elicited, human antibody 1D12 in complex with an H7 SH13 HA trimer
EMD-21961
Single-particle2.76 Å
Deposition: 11/05/2020Map released: 09/06/2021
Last modified: 20/11/2024
Sample Organism:
Homo sapiens,
Influenza A virus (A/Shanghai/JS01/2013(H7N9)),
Influenza A virus
Sample: 1D12 in complex with an H7 SH13 HA trimer
Fitted models: 6wxl (Avg. Q-score: 0.594)
Deposition Authors: Gorman J
,
Kwong PD
Sample: 1D12 in complex with an H7 SH13 HA trimer
Fitted models: 6wxl (Avg. Q-score: 0.594)
Deposition Authors: Gorman J
,
Kwong PD
Structure of an influenza group 2-neutralizing antibody targeting the hemagglutinin stem supersite.
Cheung CS,
Gorman J ,
Andrews SF,
Rawi R,
Reveiz M,
Shen CH,
Wang Y,
Harris DR ,
Nazzari AF,
Olia AS,
Raab J,
Teng IT,
Verardi R,
Wang S,
Yang Y,
Chuang GY,
McDermott AB,
Zhou T,
Kwong PD
(2022) Structure
,
Andrews SF,
Rawi R,
Reveiz M,
Shen CH,
Wang Y,
Harris DR ,
Nazzari AF,
Olia AS,
Raab J,
Teng IT,
Verardi R,
Wang S,
Yang Y,
Chuang GY,
McDermott AB,
Zhou T,
Kwong PD
(2022) Structure
Abstract:
Several influenza antibodies with broad group 2 neutralization have recently been isolated. Here, we analyze the structure, class, and binding of one of these antibodies from an H7N9 vaccine trial, 315-19-1D12. The cryo-EM structure of 315-19-1D12 Fab in complex with the hemagglutinin (HA) trimer revealed the antibody to recognize the helix A region of the HA stem, at the supersite of vulnerability recognized by group 1-specific and by cross-group-neutralizing antibodies. 315-19-1D12 was derived from HV1-2 and KV2-28 genes and appeared to form a new antibody class. Bioinformatic analysis indicated its group 2 neutralization specificity to be a consequence of four key residue positions. We specifically tested the impact of the group 1-specific N33 glycan, which decreased but did not abolish group 2 binding of 315-19-1D12. Overall, this study highlights the recognition of a broad group 2-neutralizing antibody, revealing unexpected diversity in neutralization specificity for antibodies that recognize the HA stem supersite.
Several influenza antibodies with broad group 2 neutralization have recently been isolated. Here, we analyze the structure, class, and binding of one of these antibodies from an H7N9 vaccine trial, 315-19-1D12. The cryo-EM structure of 315-19-1D12 Fab in complex with the hemagglutinin (HA) trimer revealed the antibody to recognize the helix A region of the HA stem, at the supersite of vulnerability recognized by group 1-specific and by cross-group-neutralizing antibodies. 315-19-1D12 was derived from HV1-2 and KV2-28 genes and appeared to form a new antibody class. Bioinformatic analysis indicated its group 2 neutralization specificity to be a consequence of four key residue positions. We specifically tested the impact of the group 1-specific N33 glycan, which decreased but did not abolish group 2 binding of 315-19-1D12. Overall, this study highlights the recognition of a broad group 2-neutralizing antibody, revealing unexpected diversity in neutralization specificity for antibodies that recognize the HA stem supersite.