8ZYM

Complex structure of 60 Fab bound to DS2 prefusion F trimer

Summary for 8ZYM

• Entry DOI: 10.2210/pdb8zym/pdb
• EMDB information: 60572
• Descriptor: Fusion glycoprotein F0,Expression tag, antibody light chain, antidody heavy chain, ... (4 entities in total)
• Functional Keywords: respiratory syncytial virus; prefusion f protein;ds2;antibody, viral protein/immune system, viral protein-immune system complex
• Biological source: Respiratory syncytial virus A2; More
• Total number of polymer chains: 9
• Total formula weight: 260147.96

Authors

Wang, X.,Ge, J.,Guo, F. (deposition date: 2024-06-18, release date: 2025-04-30)

Primary citation

Yang, Y.,Wang, R.,Guo, F.,Zhao, T.,Lei, Y.,Yang, Q.,Zeng, Y.,Yang, Z.,Ajavavarakula, T.,Tan, R.,Li, M.,Dong, H.,Niu, M.,Bao, K.,Geng, H.,Lv, Q.,Zhang, Q.,Shi, X.,Liu, P.,Ge, J.,Wang, X.,Zhang, L.
DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection.
Npj Vaccines, 9:258-258, 2024

PubMed Abstract: DS-Cav1, SC-TM, and DS2 are distinct designer pre-fusion F proteins (pre-F) of respiratory syncytial virus (RSV) developed for vaccines. However, their immunogenicity has not been directly compared. In this study, we generated three recombinant vaccines using the chimpanzee adenovirus vector AdC68 to express DS-Cav1, SC-TM, and DS2. All three vaccines elicited robust serum binding and neutralizing antibodies following intramuscular priming and boosting. DS2 induced the strongest antibody responses, followed by SC-TM and DS-Cav1. DS2 also provided strong protection against live RSV challenge. Monoclonal antibodies (mAbs) isolated from long-lived antibody-secreting cells (ASCs) in the bone marrow six months post-immunization with AdC68-DS2 predominantly targeted site Ø as well as site II. One neutralizing antibody against site II, mAb60, conferred strong protection against live RSV infection in mice. These findings highlight the strong ability of the DS2 design in eliciting long-lived antibody responses and guide the development of next-generation RSV vaccines.

PubMed: 39741146
DOI: 10.1038/s41541-024-01059-9

Experimental method

ELECTRON MICROSCOPY (3.23 Å)