9KVF

Cryo-EM structure of SARS-CoV-2 EG.1 spike protein in complex with triple-nAb 4A5, 4C1 and 2E10

Summary for 9KVF

• Entry DOI: 10.2210/pdb9kvf/pdb
• EMDB information: 62592
• Descriptor: 2E10 light chain, Spike protein S1, 4C1 heavy chain, ... (7 entities in total)
• Functional Keywords: sars-cov-2, neutralizing antibody, cryo-em, viral protein/immune system, viral protein-immune system complex
• Biological source: Macaca mulatta; More
• Total number of polymer chains: 7
• Total formula weight: 107793.63

Authors

Sun, H.,Jiang, Y.,Wang, S.,Zheng, Z.,Li, S.,Zheng, Q. (deposition date: 2024-12-05, release date: 2025-08-20, Last modification date: 2026-09-02)

Primary citation

Wang, S.,Sun, H.,Wang, Y.,Wang, Z.,Yuan, L.,Guo, H.,Gao, J.,Lan, M.,Wu, Y.,Shang, H.,Chen, X.,Chen, Z.,Hu, J.,Tang, Z.,Wen, G.,Ying, D.,Liu, C.,Jiang, Y.,Su, J.,Lin, M.,Wu, T.,Li, S.,Zhang, T.,Zhang, J.,Guan, Y.,Xia, N.,Yuan, Q.,Zheng, Q.,Zhang, Y.,Zheng, Z.
Broad neutralizing antibody response of a monomeric spike-based SARS-CoV-2 bivalent vaccine against diverse variants.
Proc.Natl.Acad.Sci.USA, 122:e2503254122-e2503254122, 2025

PubMed Abstract: severeacute respiratory syndrome coronavirus 2 (SARS-CoV-2) bivalent vaccines show potential against variants but lack a full understanding of the immunological mechanisms that drive broadly neutralizing antibodies (bnAbs). This study explored the immunogenicity of a bivalent vaccine in rhesus macaques, containing spike (S) proteins from the prototype (S) and chimeric S protein (S). The vaccine induced bnAbs against multiple variants, including challenging subvariants like EG.1, BA.2.86, and JN.1. The monomeric S protein exposed less accessible regions within the receptor-binding domain (RBD) "inner face" and "NTD face" and subdomains 1, eliciting a diverse array of bnAbs against various Omicron subvariants. Notably, antibodies targeting the conserved RBD inner face, such as 4A5, showed potent neutralization across all tested variants. Structural analyses provide insights into the broad protectiveness of these vaccine-elicited nAbs. This study underscores the potential of bivalent vaccines with monomeric spike proteins to confer broad-spectrum immunity, offering a promising direction for future SARS-CoV-2 universal vaccine design.

PubMed: 40854137
DOI: 10.1073/pnas.2503254122

Experimental method

ELECTRON MICROSCOPY (3 Å)