8WZ4

Cryo-EM structure of prefusion-stabilized RSV F (DS-Cav1 strain: A2) in complex with nAb 5B11 (localized refinement)

Summary for 8WZ4

• Entry DOI: 10.2210/pdb8wz4/pdb
• EMDB information: 37946
• Descriptor: RSV Fusion glycoprotein, 5B11 Fab Heavy Chain, 5B11 Fab Light Chain (3 entities in total)
• Functional Keywords: antibody, viral protein
• Biological source: Human respiratory syncytial virus A2; More
• Total number of polymer chains: 3
• Total formula weight: 79202.92

Authors

Liu, L.,Sun, H.,Sun, Y.,Zheng, Q.,Li, S.,Zheng, Z.,Xia, N. (deposition date: 2023-11-01, release date: 2024-11-06, Last modification date: 2025-06-04)

Primary citation

Sun, Y.,Liu, L.,Qiang, H.,Sun, H.,Jiang, Y.,Ren, L.,Jiang, Z.,Lei, S.,Chen, L.,Wang, Y.,Lin, X.,Wang, G.,Huang, Y.,Fu, Y.,Shi, Y.,Chen, X.,Yu, H.,Li, S.,Luo, W.,Liu, E.,Zheng, Q.,Zheng, Z.,Xia, N.
A potent broad-spectrum neutralizing antibody targeting a conserved region of the prefusion RSV F protein.
Nat Commun, 15:10085-10085, 2024

PubMed Abstract: Respiratory syncytial virus (RSV) poses a significant public health challenge, especially among children. Although palivizumab and nirsevimab, neutralizing antibodies (nAbs) targeting the RSV F protein, have been used for prophylaxis, their limitations underscore the need for more effective alternatives. Herein, we present a potent and broad nAb, named 5B11, which exhibits nanogram level of unbiased neutralizing activities against both RSV-A and -B subgroups. Notably, 5B11 shows a ~20-fold increase in neutralizing efficacy compared to 1129 (the murine precursor of palivizumab) and approximately a 3-fold increase in neutralizing efficacy against B18537 in comparison to nirsevimab. Cryo-electron microscopy analysis reveals 5B11's mechanism of action by targeting a highly conserved epitope within site V, offering a promising strategy with potentially lower risk of escape mutants. Antiviral testing in a female cotton rat model demonstrated that low-dose (1.5 mg/kg) administration of 5B11 achieved comparable prophylactic efficacy to that achieved by high-dose (15 mg/kg) of 1129. Furthermore, the humanized 5B11 showed a superior in vivo antiviral activity against B18537 infection compared to nirsevimab and palivizumab. Therefore, 5B11 is a promising RSV prophylactic candidate applicable to broad prevention of RSV infection.

PubMed: 39572535
DOI: 10.1038/s41467-024-54384-x

Experimental method

ELECTRON MICROSCOPY (3.13 Å)