Anti-Idiotypic Antibody as a Booster Vaccine Against Respiratory Syncytial Virus

<b>Background/Objectives:</b> 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...

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Main Authors: Shreya Mukhopadhyay, Ioannis Manolaridis, Christopher Warren, Aimin Tang, Gregory O’Donnell, Bin Luo, Ryan P. Staupe, Kalpit A. Vora, Zhifeng Chen
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/1/35
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Summary:<b>Background/Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> These results suggest that anti-IDs could be potentially used as booster vaccines for specific epitopes.
ISSN:2076-393X