9ZT7

SARS-CoV-2 S2 in complex with COV2-2509

Summary for 9ZT7

• Entry DOI: 10.2210/pdb9zt7/pdb
• EMDB information: 74739
• Descriptor: COV2-2509 Fab-Heavy chain, COV2-2509 Fab-Light chain, Spike protein S2, ... (5 entities in total)
• Functional Keywords: sars-cov-2, coronavirus, immune system, antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 5
• Total formula weight: 209406.74

Authors

Park, S.,Ward, A.B. (deposition date: 2025-12-23, release date: 2026-03-11)

Primary citation

Park, S.,Mischka, J.,Okba, N.,Abbad, A.,Yuan, M.,Srivastava, K.,Gleason, C.,Mulder, L.C.F.,Copps, J.,Saam, K.,Bangaru, S.,Krammer, F.,Wilson, I.A.,Simon, V.,Ward, A.B.
The buried S2 apex of SARS-CoV-2 spike elicits an immunodominant germline-restricted public antibody response.
Biorxiv, 2026

PubMed Abstract: The continued mutational pressure on the SARS-CoV-2 S1 subunit underscores the need to target the conserved S2 region for pan-coronavirus vaccine development. A detailed molecular understanding of S2-directed immune responses is therefore essential. In this study, we identified the S2 apex as the most immunodominant epitope within the S2 subunit, eliciting robust antibody responses despite occlusion by S1, using electron-microscopy-based polyclonal epitope mapping (EMPEM) of plasma from infected and vaccinated individuals. Structure-guided sequence analysis with antibody databases revealed that antibodies targeting a poorly characterized S2 Apex-B site form a convergent public clonotype, which is predominantly derived from the IGHV3-30 germline with a 14-residue CDRH3 containing a G/S-G-S/N-Y motif. This clonotype is extensively expanded, accounting for up to 40% of total spike-reactive antibody sequence counts in individual vaccinated donors. This study elucidates the molecular basis the high-frequency elicitation of this non-neutralizing clonotype emphasizing that its immunodominance acts as a primary hurdle for universal coronavirus vaccines and underscore the need for precision antigen design to redirect immunity toward more potent neutralizing targets.

PubMed: 41756886
DOI: 10.64898/2026.02.18.706653

Experimental method

ELECTRON MICROSCOPY (3.11 Å)