tetano
Editor, Senior Moderator
Structure
. 2024 Sep 15:S0969-2126(24)00369-1.
doi: 10.1016/j.str.2024.08.022. Online ahead of print. Discovery and characterization of a pan-betacoronavirus S2-binding antibody
Nicole V Johnson[SUP] 1 [/SUP], Steven C Wall[SUP] 2 [/SUP], Kevin J Kramer[SUP] 2 [/SUP], Clinton M Holt[SUP] 3 [/SUP], Sivakumar Periasamy[SUP] 4 [/SUP], Simone I Richardson[SUP] 5 [/SUP], Nelia P Manamela[SUP] 5 [/SUP], Naveenchandra Suryadevara[SUP] 6 [/SUP], Emanuele Andreano[SUP] 7 [/SUP], Ida Paciello[SUP] 7 [/SUP], Giulio Pierleoni[SUP] 7 [/SUP], Giulia Piccini[SUP] 8 [/SUP], Ying Huang[SUP] 9 [/SUP], Pan Ge[SUP] 10 [/SUP], James D Allen[SUP] 10 [/SUP], Naoko Uno[SUP] 11 [/SUP], Andrea R Shiakolas[SUP] 2 [/SUP], Kelsey A Pilewski[SUP] 2 [/SUP], Rachel S Nargi[SUP] 6 [/SUP], Rachel E Sutton[SUP] 6 [/SUP], Alexandria A Abu-Shmais[SUP] 2 [/SUP], Robert Parks[SUP] 12 [/SUP], Barton F Haynes[SUP] 13 [/SUP], Robert H Carnahan[SUP] 14 [/SUP], James E Crowe Jr[SUP] 15 [/SUP], Emanuele Montomoli[SUP] 16 [/SUP], Rino Rappuoli[SUP] 17 [/SUP], Alexander Bukreyev[SUP] 4 [/SUP], Ted M Ross[SUP] 18 [/SUP], Giuseppe A Sautto[SUP] 19 [/SUP], Jason S McLellan[SUP] 20 [/SUP], Ivelin S Georgiev[SUP] 21 [/SUP]
Affiliations
The continued emergence of deadly human coronaviruses from animal reservoirs highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq), we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryoelectron microscopy (cryo-EM) structure of 54043-5 bound to the prefusion S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses in vitro, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit.
Keywords: LALA-PG; LIBRA-seq; S2 subunit; antibodies; betacoronaviruses; coronaviruses; cryo-EM; spike protein.
. 2024 Sep 15:S0969-2126(24)00369-1.
doi: 10.1016/j.str.2024.08.022. Online ahead of print. Discovery and characterization of a pan-betacoronavirus S2-binding antibody
Nicole V Johnson[SUP] 1 [/SUP], Steven C Wall[SUP] 2 [/SUP], Kevin J Kramer[SUP] 2 [/SUP], Clinton M Holt[SUP] 3 [/SUP], Sivakumar Periasamy[SUP] 4 [/SUP], Simone I Richardson[SUP] 5 [/SUP], Nelia P Manamela[SUP] 5 [/SUP], Naveenchandra Suryadevara[SUP] 6 [/SUP], Emanuele Andreano[SUP] 7 [/SUP], Ida Paciello[SUP] 7 [/SUP], Giulio Pierleoni[SUP] 7 [/SUP], Giulia Piccini[SUP] 8 [/SUP], Ying Huang[SUP] 9 [/SUP], Pan Ge[SUP] 10 [/SUP], James D Allen[SUP] 10 [/SUP], Naoko Uno[SUP] 11 [/SUP], Andrea R Shiakolas[SUP] 2 [/SUP], Kelsey A Pilewski[SUP] 2 [/SUP], Rachel S Nargi[SUP] 6 [/SUP], Rachel E Sutton[SUP] 6 [/SUP], Alexandria A Abu-Shmais[SUP] 2 [/SUP], Robert Parks[SUP] 12 [/SUP], Barton F Haynes[SUP] 13 [/SUP], Robert H Carnahan[SUP] 14 [/SUP], James E Crowe Jr[SUP] 15 [/SUP], Emanuele Montomoli[SUP] 16 [/SUP], Rino Rappuoli[SUP] 17 [/SUP], Alexander Bukreyev[SUP] 4 [/SUP], Ted M Ross[SUP] 18 [/SUP], Giuseppe A Sautto[SUP] 19 [/SUP], Jason S McLellan[SUP] 20 [/SUP], Ivelin S Georgiev[SUP] 21 [/SUP]
Affiliations
- PMID: 39326419
- DOI: 10.1016/j.str.2024.08.022
The continued emergence of deadly human coronaviruses from animal reservoirs highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq), we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryoelectron microscopy (cryo-EM) structure of 54043-5 bound to the prefusion S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses in vitro, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit.
Keywords: LALA-PG; LIBRA-seq; S2 subunit; antibodies; betacoronaviruses; coronaviruses; cryo-EM; spike protein.