학술논문
Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody against antigenically distinct Omicron subvariants
Document Type
article
Author
Siriruk Changrob; Peter J. Halfmann; Hejun Liu; Jonathan L. Torres; Joshua J.C. McGrath; Gabriel Ozorowski; Lei Li; G. Dewey Wilbanks; Makoto Kuroda; Tadashi Maemura; Min Huang; Nai-Ying Zheng; Hannah L. Turner; Steven A. Erickson; Yanbin Fu; Atsuhiro Yasuhara; Gagandeep Singh; Brian Monahan; Jacob Mauldin; Komal Srivastava; Viviana Simon; Florian Krammer; D. Noah Sather; Andrew B. Ward; Ian A. Wilson; Yoshihiro Kawaoka; Patrick C. Wilson
Source
The Journal of Clinical Investigation, Vol 133, Iss 8 (2023)
Subject
Language
English
ISSN
1558-8238
Abstract
The rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identified S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) that was derived from an individual previously infected with WT SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrated broad cross-neutralization of all dominant variants, including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1/XBB). Furthermore, S728-1157 protected hamsters against in vivo challenges with WT, Delta, and BA.1 viruses. Structural analysis showed that this antibody targets a class 1/RBS-A epitope in the receptor binding domain via multiple hydrophobic and polar interactions with its heavy chain complementarity determining region 3 (CDR-H3), in addition to common motifs in CDR-H1/CDR-H2 of class 1/RBS-A antibodies. Importantly, this epitope was more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared with diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential and may inform target-driven vaccine designs against future SARS-CoV-2 variants.