9MML

RB1 Fab bound to 1A6 anti-idiotype Fab

Summary for 9MML

• Entry DOI: 10.2210/pdb9mml/pdb
• Related: 6OUS
• EMDB information: 48393
• Descriptor: 1A6 heavy chain, 1A6 light chain, RB1 heavy chain, ... (4 entities in total)
• Functional Keywords: fab anti idiotype rsv, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 94249.87

Authors

Warren, C. (deposition date: 2024-12-20, release date: 2025-01-08, Last modification date: 2025-02-05)

Primary citation

Mukhopadhyay, S.,Manolaridis, I.,Warren, C.,Tang, A.,O'Donnell, G.,Luo, B.,Staupe, R.P.,Vora, K.A.,Chen, Z.
Anti-Idiotypic Antibody as a Booster Vaccine Against Respiratory Syncytial Virus.
Vaccines (Basel), 13:-, 2025

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 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.

PubMed: 39852814
DOI: 10.3390/vaccines13010035

Experimental method

ELECTRON MICROSCOPY (3.67 Å)