tetano
Editor, Senior Moderator
Sci Rep
. 2022 Nov 22;12(1):20120.
doi: 10.1038/s41598-022-24730-4.
Human antibody recognition and neutralization mode on the NTD and RBD domains of SARS-CoV-2 spike protein
Ryota Otsubo[SUP] #[/SUP][SUP] 1 [/SUP], Takeharu Minamitani[SUP] #[/SUP][SUP] 1 2 [/SUP], Kouji Kobiyama[SUP] 3 4 [/SUP], Junso Fujita[SUP] 5 6 [/SUP], Toshihiro Ito[SUP] 7 8 [/SUP], Shiori Ueno[SUP] 9 [/SUP], Itsuki Anzai[SUP] 10 [/SUP], Hiroki Tanino[SUP] 6 [/SUP], Hiroshi Aoyama[SUP] 6 [/SUP], Yoshiharu Matsuura[SUP] 11 12 [/SUP], Keiichi Namba[SUP] 5 13 14 [/SUP], Ken-Ichi Imadome[SUP] 15 [/SUP], Ken J Ishii[SUP] 3 4 [/SUP], Kouhei Tsumoto[SUP] 16 17 18 [/SUP], Wataru Kamitani[SUP] 9 [/SUP], Teruhito Yasui[SUP] 19 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Variants of concern (VOCs) such as Delta and Omicron have developed, which continue to spread the pandemic. It has been reported that these VOCs reduce vaccine efficacy and evade many neutralizing monoclonal antibodies (mAbs) that target the receptor binding domain (RBD) of the glycosylated spike (S) protein, which consists of the S1 and S2 subunits. Therefore, identification of optimal target regions is required to obtain neutralizing antibodies that can counter VOCs. Such regions have not been identified to date. We obtained 2 mAbs, NIBIC-71 and 7G7, using peripheral blood mononuclear cells derived from volunteers who recovered from COVID-19. Both mAbs had neutralizing activity against wild-type SARS-CoV-2 and Delta, but not Omicron. NIBIC-71 binds to the RBD, whereas 7G7 recognizes the N-terminal domain of the S1. In particular, 7G7 inhibited S1/S2 cleavage but not the interaction between the S protein and angiotensin-converting enzyme 2; it suppressed viral entry. Thus, the efficacy of a neutralizing mAb targeting inhibition of S1/2 cleavage was demonstrated. These results suggest that neutralizing mAbs targeting blockade of S1/S2 cleavage are likely to be cross-reactive against various VOCs.
. 2022 Nov 22;12(1):20120.
doi: 10.1038/s41598-022-24730-4.
Human antibody recognition and neutralization mode on the NTD and RBD domains of SARS-CoV-2 spike protein
Ryota Otsubo[SUP] #[/SUP][SUP] 1 [/SUP], Takeharu Minamitani[SUP] #[/SUP][SUP] 1 2 [/SUP], Kouji Kobiyama[SUP] 3 4 [/SUP], Junso Fujita[SUP] 5 6 [/SUP], Toshihiro Ito[SUP] 7 8 [/SUP], Shiori Ueno[SUP] 9 [/SUP], Itsuki Anzai[SUP] 10 [/SUP], Hiroki Tanino[SUP] 6 [/SUP], Hiroshi Aoyama[SUP] 6 [/SUP], Yoshiharu Matsuura[SUP] 11 12 [/SUP], Keiichi Namba[SUP] 5 13 14 [/SUP], Ken-Ichi Imadome[SUP] 15 [/SUP], Ken J Ishii[SUP] 3 4 [/SUP], Kouhei Tsumoto[SUP] 16 17 18 [/SUP], Wataru Kamitani[SUP] 9 [/SUP], Teruhito Yasui[SUP] 19 [/SUP]
Affiliations
- PMID: 36418391
- DOI: 10.1038/s41598-022-24730-4
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Variants of concern (VOCs) such as Delta and Omicron have developed, which continue to spread the pandemic. It has been reported that these VOCs reduce vaccine efficacy and evade many neutralizing monoclonal antibodies (mAbs) that target the receptor binding domain (RBD) of the glycosylated spike (S) protein, which consists of the S1 and S2 subunits. Therefore, identification of optimal target regions is required to obtain neutralizing antibodies that can counter VOCs. Such regions have not been identified to date. We obtained 2 mAbs, NIBIC-71 and 7G7, using peripheral blood mononuclear cells derived from volunteers who recovered from COVID-19. Both mAbs had neutralizing activity against wild-type SARS-CoV-2 and Delta, but not Omicron. NIBIC-71 binds to the RBD, whereas 7G7 recognizes the N-terminal domain of the S1. In particular, 7G7 inhibited S1/S2 cleavage but not the interaction between the S protein and angiotensin-converting enzyme 2; it suppressed viral entry. Thus, the efficacy of a neutralizing mAb targeting inhibition of S1/2 cleavage was demonstrated. These results suggest that neutralizing mAbs targeting blockade of S1/S2 cleavage are likely to be cross-reactive against various VOCs.