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An Improved and High Throughput Respiratory Syncytial Virus RSV Micro-neutralization Assay
Published on: January 26, 2019
Anti-Idiotypic Antibody as a Booster Vaccine Against Respiratory Syncytial Virus
Shreya Mukhopadhyay1, Ioannis Manolaridis2, Christopher Warren1
1Infectious Diseases and Vaccine Research, Merck & Co., Inc., Rahway, NJ 07065, USA.
Insights
Anti-idiotypic antibodies (anti-IDs) show promise as booster vaccines. These antibodies mimic respiratory syncytial virus (RSV) epitopes, enhancing pre-existing immunity and increasing RSV neutralization in preclinical studies.
Area of Science:
- Immunology
- Virology
- Vaccine Development
Background:
- Respiratory syncytial virus (RSV) causes widespread infections, necessitating improved vaccines.
- Booster vaccines enhancing B-cell immunity and broadly neutralizing antibodies are needed.
- Anti-idiotypic antibodies (anti-IDs) offer a strategy to mimic viral epitopes and boost immunity.
Purpose of the Study:
- To investigate anti-IDs as potential booster vaccines against RSV.
- To evaluate the ability of anti-IDs to mimic the RSV fusion (F) protein site IV.
- To assess the immunogenicity and neutralizing capacity of anti-ID boosted responses.
Main Methods:
- Isolation of anti-idiotypic antibodies (1A6, 1D4) targeting the RB1 monoclonal antibody.
- Resolution of complex structures (RB1-1A6, RB1-1D4 Fab-Fab) to assess epitope mimicry.
- Immunogenicity studies in mice using RSV F priming and anti-ID boosting.
Main Results:
- The anti-ID 1A6 demonstrated superior mimicry of the RSV F protein site IV compared to 1D4.
- 1A6 competed with RSV F for binding to the RB1 antibody.
- Mice boosted with 1A6 Fab exhibited site IV-specific antibodies and increased RSV neutralization.
Conclusions:
- Anti-idiotypic antibodies can effectively mimic specific viral epitopes.
- Anti-IDs hold potential as a novel strategy for RSV booster vaccines.
- This approach may enhance epitope-specific immunity and viral neutralization.
Abstract:
Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: These results suggest that anti-IDs could be potentially used as booster vaccines for specific epitopes.
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