tetano
Editor, Senior Moderator
J Clin Invest
. 2023 Mar 2;e166844.
doi: 10.1172/JCI166844. Online ahead of print.
Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody to antigenically distinct Omicron subvariants
Siriruk Changrob[SUP] 1 [/SUP], Peter J Halfmann[SUP] 2 [/SUP], Hejun Liu[SUP] 3 [/SUP], Jonathan L Torres[SUP] 3 [/SUP], Joshua Jc McGrath[SUP] 1 [/SUP], Gabriel Ozorowski[SUP] 3 [/SUP], Lei Li[SUP] 1 [/SUP], G Dewey Wilbanks[SUP] 1 [/SUP], Makoto Kuroda[SUP] 2 [/SUP], Tadashi Maemura[SUP] 2 [/SUP], Min Huang[SUP] 1 [/SUP], Nai-Ying Zheng[SUP] 1 [/SUP], Hannah L Turner[SUP] 3 [/SUP], Steven A Erickson[SUP] 4 [/SUP], Yanbin Fu[SUP] 1 [/SUP], Atsuhiro Yasuhara[SUP] 1 [/SUP], Gagandeep Singh[SUP] 5 [/SUP], Brian Monahan[SUP] 5 [/SUP], Jacob Mauldin[SUP] 5 [/SUP], Komal Srivastava[SUP] 5 [/SUP], Viviana Simon[SUP] 5 [/SUP], Florian Krammer[SUP] 6 [/SUP], D Noah Sather[SUP] 7 [/SUP], Andrew B Ward[SUP] 3 [/SUP], Ian A Wilson[SUP] 3 [/SUP], Yoshihiro Kawaoka[SUP] 2 [/SUP], Patrick C Wilson[SUP] 8 [/SUP]
Affiliations
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 wildtype 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 wildtype, Delta, and BA.1 viruses. Structural analysis showed that this antibody targets a class 1/RBS-A epitope in the receptor binding domain (RBD) via multiple hydrophobic and polar interactions with its heavy chain complementarity determining region 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 to diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential, and may inform target-driven vaccine design against future SARS-CoV-2 variants.
Keywords: Adaptive immunity; COVID-19; Immunoglobulins; Immunology.
. 2023 Mar 2;e166844.
doi: 10.1172/JCI166844. Online ahead of print.
Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody to antigenically distinct Omicron subvariants
Siriruk Changrob[SUP] 1 [/SUP], Peter J Halfmann[SUP] 2 [/SUP], Hejun Liu[SUP] 3 [/SUP], Jonathan L Torres[SUP] 3 [/SUP], Joshua Jc McGrath[SUP] 1 [/SUP], Gabriel Ozorowski[SUP] 3 [/SUP], Lei Li[SUP] 1 [/SUP], G Dewey Wilbanks[SUP] 1 [/SUP], Makoto Kuroda[SUP] 2 [/SUP], Tadashi Maemura[SUP] 2 [/SUP], Min Huang[SUP] 1 [/SUP], Nai-Ying Zheng[SUP] 1 [/SUP], Hannah L Turner[SUP] 3 [/SUP], Steven A Erickson[SUP] 4 [/SUP], Yanbin Fu[SUP] 1 [/SUP], Atsuhiro Yasuhara[SUP] 1 [/SUP], Gagandeep Singh[SUP] 5 [/SUP], Brian Monahan[SUP] 5 [/SUP], Jacob Mauldin[SUP] 5 [/SUP], Komal Srivastava[SUP] 5 [/SUP], Viviana Simon[SUP] 5 [/SUP], Florian Krammer[SUP] 6 [/SUP], D Noah Sather[SUP] 7 [/SUP], Andrew B Ward[SUP] 3 [/SUP], Ian A Wilson[SUP] 3 [/SUP], Yoshihiro Kawaoka[SUP] 2 [/SUP], Patrick C Wilson[SUP] 8 [/SUP]
Affiliations
- PMID: 36862518
- DOI: 10.1172/JCI166844
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 wildtype 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 wildtype, Delta, and BA.1 viruses. Structural analysis showed that this antibody targets a class 1/RBS-A epitope in the receptor binding domain (RBD) via multiple hydrophobic and polar interactions with its heavy chain complementarity determining region 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 to diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential, and may inform target-driven vaccine design against future SARS-CoV-2 variants.
Keywords: Adaptive immunity; COVID-19; Immunoglobulins; Immunology.