7WP8

Cryo-EM structure of SARS-CoV-2 recombinant spike protein STFK1628x in complex with three neutralizing antibodies

Summary for 7WP8

• Entry DOI: 10.2210/pdb7wp8/pdb
• EMDB information: 32678
• Descriptor: 83H7 light chain, 83H7 heavy chain, 2B4 heavy chain, ... (9 entities in total)
• Functional Keywords: sars-cov-2, spike, vaccine, neutralizing antibody, cryo-em, viral protein, immune system-viral protein complex, immune system/viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 7
• Total formula weight: 96474.25

Authors

Zheng, Q.,Sun, H.,Yuan, Q.,Li, S.,Xia, N. (deposition date: 2022-01-23, release date: 2023-03-08, Last modification date: 2024-10-09)

Primary citation

Wu, Y.,Wang, S.,Zhang, Y.,Yuan, L.,Zheng, Q.,Wei, M.,Shi, Y.,Wang, Z.,Ma, J.,Wang, K.,Nie, M.,Xiao, J.,Huang, Z.,Chen, P.,Guo, H.,Lan, M.,Xu, J.,Hou, W.,Hong, Y.,Chen, D.,Sun, H.,Xiong, H.,Zhou, M.,Liu, C.,Guo, W.,Guo, H.,Gao, J.,Gan, C.,Li, Z.,Zhang, H.,Wang, X.,Li, S.,Cheng, T.,Zhao, Q.,Chen, Y.,Wu, T.,Zhang, T.,Zhang, J.,Cao, H.,Zhu, H.,Yuan, Q.,Guan, Y.,Xia, N.
Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine.
Cell Host Microbe, 30:1732-1744.e7, 2022

PubMed Abstract: SARS-CoV-2 spread in humans results in continuous emergence of new variants, highlighting the need for vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation-patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x) that contains key regions and residues across multiple SAR-CoV-2 variants. STFK1628x demonstrated high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine composed of STFK and STFK1628x elicited high titers of broad-spectrum neutralizing antibodies to 19 circulating SARS-CoV-2 variants, including Omicron sublineages BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5. Furthermore, this vaccine conferred robust protection against intranasal challenges by either SARS-CoV-2 ancestral strain or immune-evasive Beta and Omicron BA.1. Strikingly, vaccination with the bivalent vaccine in hamsters effectively blocked within-cage virus transmission of ancestral SARS-CoV-2, Beta variant, and Omicron BA.1 to unvaccinated sentinels. Thus, our study provided insight and antigen candidates for the development of next-generation COVID-19 vaccines.

PubMed: 36323313
DOI: 10.1016/j.chom.2022.10.011

Experimental method

ELECTRON MICROSCOPY (3.88 Å)