8DTK

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

Summary for 8DTK

• Entry DOI: 10.2210/pdb8dtk/pdb
• EMDB information: 27703
• Descriptor: Spike protein S1, DH1047 Fab Light Chain, DH1047 Fab Heavy Chain, ... (4 entities in total)
• Functional Keywords: rbd, fab, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 3
• Total formula weight: 50454.03

Authors

May, A.J.,Manne, K.,Acharya, P. (deposition date: 2022-07-25, release date: 2023-08-02, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.77 Å)