Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients

Li, Yang; Ma, Ming‐liang; Lei, Qing; Wang, Feng; Hong, Wei; Lai, Dan‐yun; Xu, Zhaowei; Zhang, Bo; Chen, Hong; Yu, Caizheng; Xue, Jun‐biao; Zheng, Yun-xiao; Wang, Xue-ning; Jiang, He‐wei; Zhang, Hainan; Qi, Huan; Guo, Shujuan; Zhang, Yandi; Lin, Xiang; Yao, Zongjie; Wu, Jiaoxiang; Sheng, Huiming; Zhang, Yanan; Wei, Hongping; Sun, Ziyong; Fan, Xionglin; Tao, Sheng-Ce

doi:10.1016/j.celrep.2021.108915

Cited by 143 publications

(190 citation statements)

References 77 publications

(97 reference statements)

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“…The peptide sequence of S1-61 is outside of the amino acid motif that contacts ACE2 so the significance of this epitope or its functional role is unclear and not described in previous studies. However, the peptide S2-78 has also been observed to be a region of immunodominance in antibody serology studies of natural SARS-CoV-2 infection [36][37][38]. Moreover, antibody response levels to this peptide have been shown to have a neutralizing activity and were associated with decreased COVID-19 disease severity [36,37].…”

Section: Discussionmentioning

confidence: 99%

“…However, the peptide S2-78 has also been observed to be a region of immunodominance in antibody serology studies of natural SARS-CoV-2 infection [36][37][38]. Moreover, antibody response levels to this peptide have been shown to have a neutralizing activity and were associated with decreased COVID-19 disease severity [36,37]. These observations raise the possibility that epitopes outside of the RBD that do not directly block the RBD-ACE2 interaction could be utilized to mitigate viral entry through other critical mechanisms.…”

Section: Discussionmentioning

confidence: 99%

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Humoral immune responses during SARS-CoV-2 mRNA vaccine administration in seropositive and seronegative individuals

Fraley

LeMaster

Geanes

et al. 2021

BMC Med

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Background The global pandemic of coronavirus disease 2019 (COVID-19) is caused by infection with the SARS-CoV-2 virus. Currently, there are three approved vaccines against SARS-CoV-2 in the USA, including two based on messenger RNA (mRNA) technology that has demonstrated high vaccine efficacy. We sought to characterize humoral immune responses, at high resolution, during immunization with the BNT162b2 (Pfizer-BioNTech) vaccine in individuals with or without prior history of natural SARS-CoV-2 infection. Methods We determined antibody responses after each dose of the BNT162b2 SARS-CoV-2 vaccine in individuals who had no prior history of SARS-CoV-2 infection (seronegative) and individuals that had previous viral infection 30–60 days prior to first vaccination (seropositive). To do this, we used both an antibody isotype-specific multiplexed bead-based binding assays targeting multiple SARS-CoV-2 viral protein antigens and an assay that identified potential SARS-CoV-2 neutralizing antibody levels. Moreover, we mapped antibody epitope specificity after immunization using SARS-CoV-2 spike protein peptide arrays. Results Antibody levels were significantly higher after a single dose in seropositive individuals compared to seronegative individuals and were comparable to levels observed in seronegative individuals after two doses. While IgG was boosted by vaccination for both seronegative and seropositive individuals, only seronegative individuals had increased IgA or IgM antibody titers after primary immunization. We identified immunodominant peptides targeted on both SARS-CoV-2 spike S1 and S2 subunits after vaccination. Conclusion These findings demonstrated the antibody responses to SARS-CoV-2 immunization in seropositive and seronegative individuals and provide support for the concept of using prior infection history as a guide for the consideration of future vaccination regimens. Moreover, we identified key epitopes on the SARS-CoV-2 spike protein that are targeted by antibodies after vaccination that could guide future vaccine and immune correlate development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Humoral immune responses during SARS-CoV-2 mRNA vaccine administration in seropositive and seronegative individuals

Fraley

LeMaster

Geanes

et al. 2021

BMC Med

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“…The least variable S2 subunit of S is an attractive target for a broad-spectrum neutralizing mAb. Although most currently identified antibodies induced by natural S2 unit were found to have no neutralizing activities 125 , more efforts should be engaged to search for potent S2-targeted neutralizing mAbs, either from convalescent COVID-19 patients or screen of sdAb libraries. Alternatively, various immune-focusing strategies can be used to prepare S2-based immunogens and elicit antibodies targeting potent neutralizing epitopes that are of low immunogenicity or cryptic within natural S proteins 126 .…”

Section: Future Perspectivesmentioning

confidence: 99%

SARS-CoV-2 cell entry and targeted antiviral development

Chen

Achi

et al. 2021

Acta Pharmaceutica Sinica B

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic coronavirus disease 2019 (COVID-19), which threatens human health and public safety. In the urgent campaign to develop anti-SARS-CoV-2 therapies, the initial entry step is one of the most appealing targets. In this review, we summarize the current understanding of SARS-CoV-2 cell entry, and the development of targeted antiviral strategies. Moreover, we speculate upon future directions toward next-generation of SARS-CoV-2 entry inhibitors during the upcoming post-pandemic era.

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“…This is in agreement with what is reported in literature, where the reactivity to short peptides was demonstrated to be highly variable among patients. 29 Therefore, the use of full‐length proteins or protein domains, characterised by a higher similarity to the native conformation of the original antigen, as well as by the parallel presence of several linear and conformational epitopes, may allow to better capture the predicted polyclonal humoral response to SARS‐CoV‐2. 30 In agreement to this, the first‐stage investigation of our study resulted in the selection of 12 candidate antigens, of which eight include different full‐length and protein domain versions of the spike protein, produced in HEK or CHO cells, and three versions of the NC, produced in E. coli .…”

Section: Discussionmentioning

confidence: 99%

Systematic evaluation of SARS‐CoV‐2 antigens enables a highly specific and sensitive multiplex serological COVID‐19 assay

et al. 2021

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Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five bestperforming antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further

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Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients

Cited by 143 publications

References 77 publications

Humoral immune responses during SARS-CoV-2 mRNA vaccine administration in seropositive and seronegative individuals

Humoral immune responses during SARS-CoV-2 mRNA vaccine administration in seropositive and seronegative individuals

SARS-CoV-2 cell entry and targeted antiviral development

Systematic evaluation of SARS‐CoV‐2 antigens enables a highly specific and sensitive multiplex serological COVID‐19 assay

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