Targeting RSV-neutralizing B cell receptors with anti-idiotypic antibodies
Samuel C. Scharffenberger,
Yu-Hsin Wan,
Leah J. Homad,
Gargi Kher,
Austin M. Haynes,
Bibhav Poudel,
Irika R. Sinha,
Nicholas Aldridge,
Ayana Pai,
Madeleine Bibby,
Crystal B. Chhan,
Amelia R. Davis,
Zoe Moodie,
Maria Belen Palacio,
Amelia Escolano,
M. Juliana McElrath,
Jim Boonyaratanakornkit,
Marie Pancera,
Andrew T. McGuire
Affiliations
Samuel C. Scharffenberger
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA
Yu-Hsin Wan
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
Leah J. Homad
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
Gargi Kher
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
Austin M. Haynes
Department of Global Health, University of Washington, Seattle, WA 98195, USA
Bibhav Poudel
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
Irika R. Sinha
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
Nicholas Aldridge
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
Ayana Pai
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
Madeleine Bibby
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
Crystal B. Chhan
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA
Amelia R. Davis
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
Zoe Moodie
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
Maria Belen Palacio
Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA
Amelia Escolano
Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA
M. Juliana McElrath
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA
Jim Boonyaratanakornkit
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA
Marie Pancera
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
Andrew T. McGuire
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA; Corresponding author
Summary: 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.
