8DTK

Structure of RBD directed antibody DH1047 in complex with SARS-CoV-2 spike: Local refinement of RBD-Fab interace

8DTK の概要

• エントリーDOI: 10.2210/pdb8dtk/pdb
• EMDBエントリー: 27703
• 分子名称: Spike protein S1, DH1047 Fab Light Chain, DH1047 Fab Heavy Chain, ... (4 entities in total)
• 機能のキーワード: rbd, fab, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 50454.03

構造登録者

May, A.J.,Manne, K.,Acharya, P. (登録日: 2022-07-25, 公開日: 2023-08-02, 最終更新日: 2024-02-28)

主引用文献

Malewana, R.D.,Stalls, V.,May, A.,Lu, X.,Martinez, D.R.,Schafer, A.,Li, D.,Barr, M.,Sutherland, L.L.,Lee, E.,Parks, R.,Beck, W.E.,Newman, A.,Bock, K.W.,Minai, M.,Nagata, B.M.,DeMarco, C.T.,Denny, T.N.,Oguin 3rd, T.H.,Rountree, W.,Wang, Y.,Mansouri, K.,Edwards, R.J.,Sempowski, G.D.,Eaton, A.,Muramatsu, H.,Henderson, R.,Tam, Y.,Barbosa, C.,Tang, J.,Cain, D.W.,Santra, S.,Moore, I.N.,Andersen, H.,Lewis, M.G.,Golding, H.,Seder, R.,Khurana, S.,Montefiori, D.C.,Pardi, N.,Weissman, D.,Baric, R.S.,Acharya, P.,Haynes, B.F.,Saunders, K.O.
Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates.
Biorxiv, 2023

PubMed Abstract: Immunization with mRNA or viral vectors encoding spike with diproline substitutions (S-2P) has provided protective immunity against severe COVID-19 disease. How immunization with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike elicits neutralizing antibodies (nAbs) against difficult-to-neutralize variants of concern (VOCs) remains an area of great interest. Here, we compare immunization of macaques with mRNA vaccines expressing ancestral spike either including or lacking diproline substitutions, and show the diproline substitutions were not required for protection against SARS-CoV-2 challenge or induction of broadly neutralizing B cell lineages. One group of nAbs elicited by the ancestral spike lacking diproline substitutions targeted the outer face of the receptor binding domain (RBD), neutralized all tested SARS-CoV-2 VOCs including Omicron XBB.1.5, but lacked cross-Sarbecovirus neutralization. Structural analysis showed that the macaque broad SARS-CoV-2 VOC nAbs bound to the same epitope as a human broad SARS-CoV-2 VOC nAb, DH1193. Vaccine-induced antibodies that targeted the RBD inner face neutralized multiple Sarbecoviruses, protected mice from bat CoV RsSHC014 challenge, but lacked Omicron variant neutralization. Thus, ancestral SARS-CoV-2 spike lacking proline substitutions encoded by nucleoside-modified mRNA can induce B cell lineages binding to distinct RBD sites that either broadly neutralize animal and human Sarbecoviruses or recent Omicron VOCs.

PubMed: 38187726
DOI: 10.1101/2023.12.18.572191

実験手法

ELECTRON MICROSCOPY (3.77 Å)