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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2025-01-01
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| author | Shreya Mukhopadhyay Ioannis Manolaridis Christopher Warren Aimin Tang Gregory O’Donnell Bin Luo Ryan P. Staupe Kalpit A. Vora Zhifeng Chen |
| author_facet | Shreya Mukhopadhyay Ioannis Manolaridis Christopher Warren Aimin Tang Gregory O’Donnell Bin Luo Ryan P. Staupe Kalpit A. Vora Zhifeng Chen |
| author_sort | Shreya Mukhopadhyay |
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| description | <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. |
| format | Article |
| id | doaj-art-b9797caf70eb47cb9a50645add0538cf |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-b9797caf70eb47cb9a50645add0538cf2025-01-24T13:51:44ZengMDPI AGVaccines2076-393X2025-01-011313510.3390/vaccines13010035Anti-Idiotypic Antibody as a Booster Vaccine Against Respiratory Syncytial VirusShreya Mukhopadhyay0Ioannis Manolaridis1Christopher Warren2Aimin Tang3Gregory O’Donnell4Bin Luo5Ryan P. Staupe6Kalpit A. Vora7Zhifeng Chen8Infectious Diseases and Vaccine Research, Merck & Co., Inc., Rahway, NJ 07065, USAProtein and Structural Chemistry, Merck & Co., Inc., Rahway, NJ 07065, USAInfectious Diseases and Vaccine Research, Merck & Co., Inc., Rahway, NJ 07065, USAInfectious Diseases and Vaccine Research, Merck & Co., Inc., Rahway, NJ 07065, USAQuantitative Biosciences, Merck & Co., Inc., Rahway, NJ 07065, USAQuantitative Biosciences, Merck & Co., Inc., Rahway, NJ 07065, USAInfectious Diseases and Vaccine Research, Merck & Co., Inc., Rahway, NJ 07065, USAInfectious Diseases and Vaccine Research, Merck & Co., Inc., Rahway, NJ 07065, USAInfectious Diseases and Vaccine Research, Merck & Co., Inc., Rahway, NJ 07065, USA<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.https://www.mdpi.com/2076-393X/13/1/35Respiratory Syncytial Virus (RSV)RSV Fusion protein (RSV F)anti-idiotypic antibodies (anti-ID)structural mimicrycryo-EMepitope-specific immunization |
| spellingShingle | Shreya Mukhopadhyay Ioannis Manolaridis Christopher Warren Aimin Tang Gregory O’Donnell Bin Luo Ryan P. Staupe Kalpit A. Vora Zhifeng Chen Anti-Idiotypic Antibody as a Booster Vaccine Against Respiratory Syncytial Virus Vaccines Respiratory Syncytial Virus (RSV) RSV Fusion protein (RSV F) anti-idiotypic antibodies (anti-ID) structural mimicry cryo-EM epitope-specific immunization |
| title | Anti-Idiotypic Antibody as a Booster Vaccine Against Respiratory Syncytial Virus |
| title_full | Anti-Idiotypic Antibody as a Booster Vaccine Against Respiratory Syncytial Virus |
| title_fullStr | Anti-Idiotypic Antibody as a Booster Vaccine Against Respiratory Syncytial Virus |
| title_full_unstemmed | Anti-Idiotypic Antibody as a Booster Vaccine Against Respiratory Syncytial Virus |
| title_short | Anti-Idiotypic Antibody as a Booster Vaccine Against Respiratory Syncytial Virus |
| title_sort | anti idiotypic antibody as a booster vaccine against respiratory syncytial virus |
| topic | Respiratory Syncytial Virus (RSV) RSV Fusion protein (RSV F) anti-idiotypic antibodies (anti-ID) structural mimicry cryo-EM epitope-specific immunization |
| url | https://www.mdpi.com/2076-393X/13/1/35 |
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