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TitleDS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection.
Journal, issue, pagesNPJ Vaccines, Vol. 9, Issue 1, Page 258, Year 2024
Publish dateDec 31, 2024
AuthorsYiling Yang / Ruoke Wang / Fenglin Guo / Tian Zhao / Yuqing Lei / Qianqian Yang / Yige Zeng / Ziqing Yang / Tatchapon Ajavavarakula / Ruijie Tan / Mingxi Li / Haodi Dong / Mengyue Niu / Keyan Bao / Hao Geng / Qining Lv / Qi Zhang / Xuanling Shi / Peng Liu / Jiwan Ge / Xinquan Wang / Linqi Zhang /
PubMed AbstractDS-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. ...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.
External linksNPJ Vaccines / PubMed:39741146 / PubMed Central
MethodsEM (single particle)
Resolution3.23 Å
Structure data

60572

8zym

EMDB-60572, PDB-8zym:
Complex structure of 60 Fab bound to DS2 prefusion F trimer
Method: EM (single particle) / Resolution: 3.23 Å

Chemicals

ChemComp-HOH:
WATER

Source
  • respiratory syncytial virus a2
  • synthetic construct (others)
  • mus musculus (house mouse)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Respiratory syncytial virus; prefusion F protein;DS2;antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex

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