6WXL

Cryo-EM structure of the VRC315 clinical trial, vaccine-elicited, human antibody 1D12 in complex with an H7 SH13 HA trimer

Summary for 6WXL

• Entry DOI: 10.2210/pdb6wxl/pdb
• EMDB information: 21961
• Descriptor: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, 1D12 Light chain, ... (5 entities in total)
• Functional Keywords: vrc, immune system, vrc315, group 2, fab
• Biological source: Influenza A virus (A/Shanghai/JS01/2013(H7N9)); More
• Total number of polymer chains: 12
• Total formula weight: 329854.32

Authors

Gorman, J.,Kwong, P.D. (deposition date: 2020-05-11, release date: 2021-06-09, Last modification date: 2024-11-20)

Primary citation

Cheung, C.S.,Gorman, J.,Andrews, S.F.,Rawi, R.,Reveiz, M.,Shen, C.H.,Wang, Y.,Harris, D.R.,Nazzari, A.F.,Olia, A.S.,Raab, J.,Teng, I.T.,Verardi, R.,Wang, S.,Yang, Y.,Chuang, G.Y.,McDermott, A.B.,Zhou, T.,Kwong, P.D.
Structure of an influenza group 2-neutralizing antibody targeting the hemagglutinin stem supersite.
Structure, 2022

PubMed 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.

PubMed: 35489332
DOI: 10.1016/j.str.2022.04.003

Experimental method

ELECTRON MICROSCOPY (2.76 Å)