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TitleAnti-Idiotypic Antibody as a Booster Vaccine Against Respiratory Syncytial Virus.
Journal, issue, pagesVaccines (Basel), Vol. 13, Issue 1, Year 2025
Publish dateJan 2, 2025
AuthorsShreya Mukhopadhyay / Ioannis Manolaridis / Christopher Warren / Aimin Tang / Gregory O'Donnell / Bin Luo / Ryan P Staupe / Kalpit A Vora / Zhifeng Chen /
PubMed Abstract The respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in children and adults. With nearly everyone infected by the age of five, there is an opportunity to ... The respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in children and adults. With nearly everyone infected by the age of five, there is an opportunity to develop booster vaccines that enhance B-cell immunity, promoting potent and broadly neutralizing antibodies. One potential approach involves using anti-idiotypic antibodies (anti-IDs) to mimic specific antigenic sites and enhance preexisting immunity in an epitope-specific manner. RB1, a monoclonal antibody (mAb) that binds to site IV of the RSV fusion (RSV F) protein, is a potent and broadly neutralizing against RSV A and B viruses. It is the precursor for MK1654 (clesrovimab), which successfully completed a Phase III clinical trial. In this study, we isolated two anti-IDs, 1A6 and 1D4, targeting RB1 CDR regions, demonstrating that 1A6 competes fully with RSV F in binding to RB1. We resolved the RB1-1A6 and RB1-1D4 Fab-Fab complex structures and proved that 1A6 mimics the RSV F site IV better than 1D4. In an immunogenicity study, mice primed with RSV F and boosted with 1A6 Fab showed a site IV-specific antibody response with a concurrent increase in RSV virus neutralization. These results suggest that anti-IDs could be potentially used as booster vaccines for specific epitopes.
External linksVaccines (Basel) / PubMed:39852814 / PubMed Central
MethodsEM (single particle)
Resolution3.67 - 3.79 Å
Structure data

48393

9mml

EMDB-48393, PDB-9mml:
RB1 Fab bound to 1A6 anti-idiotype Fab
Method: EM (single particle) / Resolution: 3.67 Å

48404

9mmv

EMDB-48404, PDB-9mmv:
RB1 Fab bound to 1D4 anti-idiotype Fab
Method: EM (single particle) / Resolution: 3.79 Å

Source
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM / Fab anti idiotype RSV

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