Targeting RSV-neutralizing B cell receptors with anti-idiotypic antibodies
Respiratory syncytial virus (RSV) causes lower respiratory tract infections with significant morbidity and mortality at the extremes of age. Vaccines based on the viral fusion protein are approved for adults over 60, but infant protection relies on passive immunity via antibody transfer or maternal vaccination. An infant vaccine that rapidly elicits protective antibodies would fulfill a critical unmet need. Antibodies arising from the VH3-21/VL1-40 gene pairing can neutralize RSV without the need for affinity maturation, making them attractive to target through vaccination. Here, we develop an anti-idiotypic monoclonal antibody (ai-mAb) immunogen that is specific for unmutated VH3-21/VL1-40 B cell receptors (BCRs). The ai-mAb efficiently engages B cells with bona fide target BCRs and does not activate off-target non-neutralizing B cells, unlike recombinant pre-fusion (preF) protein used in current RSV vaccines. These results establish proof of concept for using an ai-mAb-derived vaccine to target B cells hardwired to produce RSV-neutralizing antibodies.
Authors
- Jim Boonyaratanakornkit (ORCID: https://orcid.org/0000-0001-5858-2662)
- Zoe Moodie (ORCID: https://orcid.org/0000-0001-8701-2001)
- Amelia Escolano (ORCID: https://orcid.org/0000-0002-1945-2440)
- Madeleine Bibby
- Gargi Kher (ORCID: https://orcid.org/0000-0002-8198-2418)
- Marie Pancera (ORCID: https://orcid.org/0000-0001-9217-6270)
- Andrew T. McGuire (ORCID: https://orcid.org/0000-0003-1841-6859)
- Austin M. Haynes (ORCID: https://orcid.org/0000-0001-9122-9211)
- Irika R. Sinha (ORCID: https://orcid.org/0000-0001-6440-7019)
- Yu-Hsin Wan (ORCID: https://orcid.org/0000-0003-2826-9928)
- Samuel C. Scharffenberger (ORCID: https://orcid.org/0000-0001-5905-8862)
- M. Juliana McElrath (ORCID: https://orcid.org/0000-0003-2276-7117)
- Bibhav Poudel (ORCID: https://orcid.org/0000-0002-7631-3017)
- Leah J. Homad (ORCID: https://orcid.org/0000-0001-8421-6519)
- Crystal B. Chhan
- A. Davis (ORCID: https://orcid.org/0000-0002-6983-3567)
- Maria Belen Palacio
- Nicholas Aldridge
- Ayana Pai
Institutions
- The Wistar Institute (US)
- Infectious Disease Research Institute (US)
- University of Washington (US)
- Fred Hutch Cancer Center (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-10-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.114811
- Citations
- 8
- Primary Topic
- Viral Infections and Immunology Research
- Type
- article
- Field-Weighted Citation Impact
- 3.22
Funders
- U.S. Department of Energy
- Bill and Melinda Gates Foundation
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- University of Washington
- National Institutes of Health
- Office of Science
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases
- Biological and Environmental Research
- Argonne National Laboratory