tetano
Editor, Senior Moderator
Virol Sin
. 2021 Jul 5.
doi: 10.1007/s12250-021-00409-4. Online ahead of print.
Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants
Yuanyuan Qu[SUP] #[/SUP][SUP] 1 [/SUP], Xueyan Zhang[SUP] #[/SUP][SUP] 2 3 [/SUP], Meiyu Wang[SUP] #[/SUP][SUP] 4 5 [/SUP], Lina Sun[SUP] #[/SUP][SUP] 1 [/SUP], Yongzhong Jiang[SUP] 6 [/SUP], Cheng Li[SUP] 7 [/SUP], Wei Wu[SUP] 1 [/SUP], Zhen Chen[SUP] 2 [/SUP], Qiangling Yin[SUP] 1 [/SUP], Xiaolin Jiang[SUP] 8 [/SUP], Yang Liu[SUP] 1 [/SUP], Chuan Li[SUP] 1 [/SUP], Jiandong Li[SUP] 1 [/SUP], Tianlei Ying[SUP] 7 [/SUP], Dexin Li[SUP] 1 [/SUP], Faxian Zhan[SUP] 6 [/SUP], Youchun Wang[SUP] 4 5 [/SUP], Wuxiang Guan[SUP] 9 [/SUP], Shiwen Wang[SUP] 10 [/SUP], Mifang Liang[SUP] 11 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high-affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446-S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351, and reacted with mutations of N501Y, E484K, and L452R, indicated that it may also neutralize the recent India endemic strain B.1.617. The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants, which mitigated the risk of viral escape. Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-CoV-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-CoV-2 variants.
Keywords: Angiotensin-converting enzyme 2 (ACE2); Antibody cocktail; Broad neutralization; SARS-CoV-2 variants; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
. 2021 Jul 5.
doi: 10.1007/s12250-021-00409-4. Online ahead of print.
Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants
Yuanyuan Qu[SUP] #[/SUP][SUP] 1 [/SUP], Xueyan Zhang[SUP] #[/SUP][SUP] 2 3 [/SUP], Meiyu Wang[SUP] #[/SUP][SUP] 4 5 [/SUP], Lina Sun[SUP] #[/SUP][SUP] 1 [/SUP], Yongzhong Jiang[SUP] 6 [/SUP], Cheng Li[SUP] 7 [/SUP], Wei Wu[SUP] 1 [/SUP], Zhen Chen[SUP] 2 [/SUP], Qiangling Yin[SUP] 1 [/SUP], Xiaolin Jiang[SUP] 8 [/SUP], Yang Liu[SUP] 1 [/SUP], Chuan Li[SUP] 1 [/SUP], Jiandong Li[SUP] 1 [/SUP], Tianlei Ying[SUP] 7 [/SUP], Dexin Li[SUP] 1 [/SUP], Faxian Zhan[SUP] 6 [/SUP], Youchun Wang[SUP] 4 5 [/SUP], Wuxiang Guan[SUP] 9 [/SUP], Shiwen Wang[SUP] 10 [/SUP], Mifang Liang[SUP] 11 [/SUP]
Affiliations
- PMID: 34224110
- DOI: 10.1007/s12250-021-00409-4
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high-affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446-S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351, and reacted with mutations of N501Y, E484K, and L452R, indicated that it may also neutralize the recent India endemic strain B.1.617. The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants, which mitigated the risk of viral escape. Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-CoV-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-CoV-2 variants.
Keywords: Angiotensin-converting enzyme 2 (ACE2); Antibody cocktail; Broad neutralization; SARS-CoV-2 variants; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).