Defining a highly conserved B cell epitope in the receptor binding motif of SARS-CoV-2 spike glycoprotein
Year: 2024
Type: preprint
Abstract: SARS-CoV-2 mRNA vaccines induce robust and persistent germinal centre (GC) B cell responses in humans. It remains unclear how the continuous evolution of the virus impacts the breadth of the induced GC B cell response. Using ultrasound-guided fine needle aspiration, we examined draining lymph nodes of nine healthy adults following bivalent booster immunization. We show that 77.8% of the B cell clones in the GC expressed as representative monoclonal antibodies recognized the spike protein, with a third (37.8%) of these targeting the receptor binding domain (RBD). Strikingly, only one RBD-targeting mAb, mAb-52, neutralized all tested SARS-CoV-2 strains, including the recent KP.2 variant. mAb-52 utilizes the IGHV3-66 public clonotype, protects hamsters challenged against the EG.5.1 variant and targets the class I/II RBD epitope, closely mimicking the binding footprint of ACE2. Finally, we show that the remarkable breadth of mAb-52 is due to the somatic hypermutations accumulated within vaccine-induced GC reaction.
Authors: Sameer Kumar Malladi, Deepika Jaiswal, Baoling Ying, Wafaa B. Alsoussi, Tamarand L. Darling, Bernadeta Dadonaite, Alesandro Civljak, Stephen C. Horvath, Julian Q. Zhou, Wooseob Kim, Jackson S. Turner, Aaron J. Schmitz, Fangjie Han, Suzanne M. Scheaffer, Christopher W. Farnsworth, Raffael Nachbagauer, Biliana Nestorova, Spyros Chalkias, Michael K. Klebert, Darin K. Edwards, Robert Paris, Benjamin S. Strnad, William D. Middleton, Jane A. O’Halloran, Rachel M. Presti, Jesse D. Bloom, Adrianus C. M. Boon, Michael S. Diamond, Goran Bajic, Ali H. Ellebedy
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Big Omics Data Engine 2 Supercomputer, COVID and Translational Science supercomputer (CATS), Conduits: Mount Sinai Health System Translational Science Hub, Programming Long-lasting Immunity to Coronaviruses (PLUTO), The Development and Evaluation of Pan-Coronavirus Vaccines, Cancer Center Support Grant, Structural interrogation of vaccine- and infection-induced B cell responses
OpenAlex ID: W4405203878