9MR2

SARS-CoV-2 S2 monomer in complex with NICA01A-1401 Fab

9MR2 の概要

• エントリーDOI: 10.2210/pdb9mr2/pdb
• EMDBエントリー: 48550
• 分子名称: NICA01A-1401 Fab Heavy chain, NICA01A-1401 Fab Light chain, Spike protein S2 (3 entities in total)
• 機能のキーワード: sars-cov-2, spike, s2, covid, monoclonal antibody, complex, viral protein, viral protein-immune system complex, virus
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 77144.61

構造登録者

Park, S.,Bangaru, B.,Ward, A.B. (登録日: 2025-01-06, 公開日: 2025-11-26)

主引用文献

Changrob, S.,Yasuhara, A.,Park, S.,Bangaru, S.,Li, L.,Troxell, C.A.,Halfmann, P.J.,Erickson, S.A.,Catanzaro, N.J.,Yuan, M.,Zhou, P.,Huang, M.,Wilbanks, G.D.,McGrath, J.J.C.,Singh, G.,Nelson, S.A.,Fu, Y.,Zheng, N.Y.,Carayannopoulos, S.M.,Dugan, H.L.,Shaw, D.G.,Stamper, C.T.,Madariaga, M.L.L.,Krammer, F.,Andrabi, R.,Burton, D.R.,Ward, A.B.,Wilson, I.A.,Kawaoka, Y.,Wilson, P.C.
Common cold embecovirus imprinting primes broadly neutralizing antibody responses to SARS-CoV-2 S2.
J.Exp.Med., 222:-, 2025

PubMed Abstract: The S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is highly conserved across coronavirus strains and therefore is a potential pan-coronavirus vaccine target. However, antibodies targeting this region are typically non-neutralizing. We report herein that S2-targeting antibodies from patients who recovered from SARS-CoV-2 infection bound only closely related sarbecovirus subgenus strains and, like most known S2 antibodies, none of these were neutralizing. In contrast, first-exposure, severe acutely infected COVID-19 patients predominantly induced back-boosted antibody-secreting cells imprinted against past common cold coronavirus strain OC43 that were cross-reactive to as many as five subgenera of betacoronavirus strains and gave rise to antibodies that were neutralizing and protective. The antibodies targeted two different sites: one defined by competition with stem helix antibodies, and the second to an underdescribed epitope at the apex of S2. These findings suggest that S2-targeted vaccines could strategically exploit controlled OC43 priming followed by SARS-CoV-2 boosting to enhance the breadth and quality of protective antibody responses.

PubMed: 41066082
DOI: 10.1084/jem.20251146

実験手法

ELECTRON MICROSCOPY (3.79 Å)