Structural Basis of a Human Neutralizing Antibody Specific to the SARS-CoV-2 Spike Protein Receptor-Binding Domain

Yang, Mei; Li, Jiaqi; Huang, Zhenguo; Li, Heng; Wang, Yueming; Wang, Xiaoli; Kang, Shiyang; Huang, Xing; Wu, Changwen; Liu, Tong; Jia, Zhenxing; Liang, Junlang; Yuan, Xiaohui; He, Songtao; Chen, Xiaoxue; Zhou, Zhechong; Chen, Qiuyue; Liu, Siqi; Li, Jing; Zheng, Huiwen; Liu, Xi; Li, Kenan; Yao, Xiaojun; Liu, Bin; Liu, Longding; Liao, Hua‐Xin; Chen, Shoudeng

doi:10.1128/spectrum.01352-21

Cited by 16 publications

(11 citation statements)

References 48 publications

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“…Clinical trials have reported that several RBD-containing vaccines could induce nAbs and protect against SARS-CoV-2 infection with acceptable adverse events [ 10 , 20 , 21 , 22 ]. Moreover, conjugation to an appropriate, defined vaccine carrier or a formulation including adjuvants can be applied to a RBD domain and epitope vaccine to enhance the neutralization activity of RBD-specific Abs [ 11 , 12 , 13 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ], and universal and/or cross-recognizing epitopes encoded by mutated variants could inhibit the binding of mutated RBDs to hACE2 [ 18 , 27 , 28 , 29 , 30 ]. In addition to RBD, the membrane fusion-critical regions that form the six helix bundles of S2-HR1/HR2 should be considered as target epitopes of vaccine antigens, as these regions were found to be rarely mutated in the known variants [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Closed Linear Epitopes in S1-RBD and S2-HR1/2 of SARS-CoV-2 Spike Protein Able to Induce Neutralizing Abs

et al. 2023

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SARS-CoV-2 has evolved as several variants. Immunization to boost the Ab response to Spike antigens is effective, but similar vaccines could not enhance Ab efficacy enough. Effective Ab responses against the human ACE2 (hACE2)-mediated infection of the emerging SARS-CoV-2 variants are needed. We identified closed linear epitopes of the SARS-CoV-2 Spike molecule that induced neutralizing Abs (nAbs) against both S1-RBD, responsible for attachment to hACE2, and S2-HR1/2, in convalescents and vaccine recipients. They inhibited a pseudo-virus infection mediated by the hACE2 pathway. The epitope sequences included epitopes #7 (aa411-432), #11 (aa459-480) and #111 (aa1144-1161), in S1-RBD and S2-HR2. Epitope #111 was conserved in Wuhan and variant strains, whereas #7 and #11 were conserved in Wuhan carried mutations K417N and S477N/T478K in Omicron BA.4/5. These mutations were recognized by the original epitope-specific Abs. These epitopes in RBD and HR2 neither contained, nor overlapped with, those responsible for the antibody-dependent enhancement of the SARS-CoV-2 infection. The sublingual administration of multiple epitope-conjugated antigens increased the IgG and IgA Abs specific to the neutralizing epitopes in mice pre-immunized subcutaneously. The findings indicated that S1-RBD and S2-HR2 epitopes were responsible for pseudo-virus SARS-CoV-2 infections and that sublingual boosts with multiple epitope-conjugated antigens could enhance the protection by nAbs of IgG and IgA against infection by a wide range of variants.

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Section: Introductionmentioning

confidence: 99%

Identification of Closed Linear Epitopes in S1-RBD and S2-HR1/2 of SARS-CoV-2 Spike Protein Able to Induce Neutralizing Abs

et al. 2023

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“…Neutralizing antibodies in the nasal mucosa provide the first barrier to SARS-CoV-2 [ 29 ]. The effectiveness of mAbs in blocking SARS-CoV-2 invasion has been demonstrated in animal models [ 13 , 30 , 31 ], F61 exhibits broad neutralizing activity against VOC strains (Delta, Omicron BA.1, Omicron BA.1.1, and Omicron BA.2), providing highly effective protection in vivo with dose-sparing; thus, paving the way for its use as a universal antibody against SARS-CoV-2 mutants in humans [ 24 , 26 ]. Few studies have reported the pharmacokinetics of nasal mucosal immunization in the blood, our study revealed low serum antibody concentrations (in the picogram range) of F61 after seven days of repeated nasal mucosal administration.…”

Section: Resultsmentioning

confidence: 99%

Human monoclonal antibody F61 nasal spray effectively protected high-risk populations from SARS-CoV-2 variants during the COVID-19 pandemic from late 2022 to early 2023 in China

Liu,

Zhang,

Liu

et al. 2024

Emerging Microbes & Infections

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Following the national dynamic zero-COVID strategy adjustment, the utilization of broad-spectrum nasal neutralizing antibodies may offer an alternative approach to controlling the outbreak of Omicron variants between late 2022 and early 2023 in China. This study involved an investigator-initiated trial (IIT) to assess the pharmacokinetic, safety and efficacy of the F61 nasal spray. A total of 2,008 participants were randomly assigned to receive F61 nasal spray (24 mg/0.8 mL/dose) or normal saline (0.8 mL/dose) and 1336 completed the follow-up in the IIT. Minimal absorption of F61 antibody into the bloodstream was detected in individuals receiving F61 nasal spray for seven consecutive days. No treatment-emergent adverse reactions of grade 3 severity or higher were reported. In the one-dose cohort, the 7-day cumulative SARS-CoV-2 infection rate was 79.0% in the F61 group and 82.6% in the placebo group, whereas, in the multiple-dose (once daily for 7 consecutive days) cohort, the rates were 6.55% in the F61 group and 23.83% in the placebo group. The laboratory-confirmed efficacy of F61 was 3.78% (−3.74%–10.75%) in the one-dose cohort and 72.19% (57.33%–81.87%) in the multiple-dose cohort. In the real-world study, 60,225 volunteers in four different regions were administered the F61 nasal spray based on the subject's wishes, over 90% efficacy rate was observed against different Omicron variants. The F61 nasal spray, with its favourable safety profile, could be a promising prophylactic monoclonal antibody against SARS-CoV-2 VOCs.

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“…20 Instead, developing efficient RBD-ACE2 blockers is promising alternative. 21,37,38 In addition, several neutralizing monoclonal antibodies, such as nCoV617 (PDB: ), 39 B38 and H4 (PDB: ) 40 were suggested. The S protein stabilized by this double-proline mutation was used to develop mRNA vaccines mRNA-1273 and BNT162b2 by Moderna and Pfizer-BioNTech in December 2020 and January 2021, respectively.…”

Section: Structural and Non-structural Proteins Of Sars-cov-2mentioning

confidence: 99%

Main and papain-like proteases as prospective targets for pharmacological treatment of coronavirus SARS-CoV-2

Yevsieieva,

Lohachova,

Kyrychenko

et al. 2023

RSC Adv.

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Structural Basis of a Human Neutralizing Antibody Specific to the SARS-CoV-2 Spike Protein Receptor-Binding Domain

Abstract: COVID-19 is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has posed a serious threat to global health and the economy, so it is necessary to find safe and effective antibody drugs and treatments.

Cited by 16 publications

References 48 publications

Identification of Closed Linear Epitopes in S1-RBD and S2-HR1/2 of SARS-CoV-2 Spike Protein Able to Induce Neutralizing Abs

Identification of Closed Linear Epitopes in S1-RBD and S2-HR1/2 of SARS-CoV-2 Spike Protein Able to Induce Neutralizing Abs

Human monoclonal antibody F61 nasal spray effectively protected high-risk populations from SARS-CoV-2 variants during the COVID-19 pandemic from late 2022 to early 2023 in China

Main and papain-like proteases as prospective targets for pharmacological treatment of coronavirus SARS-CoV-2

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