SARS-CoV-2-induced humoral immunity through B cell epitope analysis in COVID-19 infected individuals

Yoshida, Shota; Ono, Chikako; Hayashi, Hiroki; Fukumoto, Shinya; Shiraishi, Satoshi; Tomono, Kazunori; Arase, Hisashi; Matsuura, Yoshiharu; Nakagami, Hironori

doi:10.1038/s41598-021-85202-9

Cited by 32 publications

(28 citation statements)

References 36 publications

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“…During the course of the present study, four of the five spike epitopes (249-261, 597-606, 805-816, 1256-1265), and three of the nine nucleoprotein epitopes (164-216, 232-269, 361-390) we predicted, were further shown by others to be regions which overlap with new epitopes identified in laboratory studies (Amrun et al, 2020;Poh et al, 2020;Shrock et al, 2020;Wang et al, 2020;Yi et al, 2020;Yoshida et al, 2021), providing support to the selected epitope mapping approach.…”

Section: Identification and Selection Of B Cell Epitopes In Sars-cov-2 Proteinssupporting

confidence: 75%

“…However, while bioinformatics studies can narrow these lists, the current study is limited to predictions alone and ultimately need to be confirmed experimentally. Since the initial epitope predictions were performed, new literature emerged to identify new SARS-CoV-2 B cell epitopes in vitro that were also identified by our approach which have not been reported previously (Amrun et al, 2020;Poh et al, 2020;Shrock et al, 2020;Wang et al, 2020;Yi et al, 2020;Yoshida et al, 2021). Several of our predicted epitopes, including: Spike 249-261, 597-606, 805-816, 1256-1265NP 164-216, 232-269, 361-390;Orf3a 172-197, 216-225, Orf8 23-45, 48-56 overlap with the new epitopes highlighted in these reports.…”

Section: Discussionmentioning

confidence: 94%

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Predicted B Cell Epitopes Highlight the Potential for COVID-19 to Drive Self-Reactive Immunity

et al. 2021

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COVID-19, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), whilst commonly characterised as a respiratory disease, is reported to have extrapulmonary manifestations in multiple organs. Extrapulmonary involvement in COVID-19 includes autoimmune-like diseases such as Guillain-Barré syndrome and Kawasaki disease, as well as the presence of various autoantibodies including those associated with autoimmune diseases such a systemic lupus erythematosus (e.g. ANA, anti-La). Multiple strains of SARS-CoV-2 have emerged globally, some of which are found to be associated with increased transmissibility and severe disease. We performed an unbiased comprehensive mapping of the potential for cross-reactivity with self-antigens across multiple SARS-CoV-2 proteins and compared identified immunogenic regions across multiples strains. Using the Immune Epitope Database (IEDB) B cell epitope prediction tool, regions predicted as antibody epitopes with high prediction scores were selected. Epitope sequences were then blasted to eight other global strains to identify mutations within these regions. Of the 15 sequences compared, eight had a mutation in at least one other global strain. Predicted epitopes were then compared to human proteins using the NCBI blast tool. In contrast to studies focusing on short sequences of peptide identity, we have taken an immunological approach to selection criteria for further analysis and have identified 136 alignments of 6–23 amino acids (aa) in 129 human proteins that are immunologically likely to be cross-reactive with SARS-CoV-2. Additionally, to identify regions with significant potential to interfere with host cell function-or promote immunopathology, we identified epitope regions more likely to be accessible to pathogenic autoantibodies in the host, selected using a novel combination of sequence similarity, and modelling protein and alignment localization with a focus on extracellular regions. Our analysis identified 11 new predicted B-cell epitopes in host proteins, potentially capable of explaining key aspects of COVID-19 extrapulmonary pathology, and which were missed in other in silico studies which used direct identity rather than immunologically related functional criteria.

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Section: Identification and Selection Of B Cell Epitopes In Sars-cov-2 Proteinssupporting

confidence: 75%

Section: Discussionmentioning

confidence: 94%

Predicted B Cell Epitopes Highlight the Potential for COVID-19 to Drive Self-Reactive Immunity

et al. 2021

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“…However, as we also observed, these tests show a variable correlation to neutralization assays. Moreover, RBD-binding or ACE2-RBD competitive assays are able to reveal an important portion of NAbs but do not measure the neutralizing activity directed against epitopes outside the RBD, such as the N-terminal domain of the S protein [34][35][36][37]. This may lead to an incorrect estimation of functional antibody-mediated immunity, espe-cially in naturally infected individuals, where a more heterogeneous response is observed, as compared to the vaccinee population.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Serum Neutralization Assay: A Traditional Tool for a Brand-New Virus

Matusali

Colavita

Lapa

et al. 2021

Viruses

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SARS-CoV-2 serum neutralization assay represents the gold standard for assessing antibody-mediated protection in naturally infected and vaccinated individuals. In the present study, 662 serum samples collected from February 2020 to January 2021 from acute and convalescent COVID-19 patients were tested to determine neutralizing antibody (NAb) titers using a microneutralization test (MNT) for live SARS-CoV-2. Moreover, anti-SARS-CoV-2 IgG, IgA, and IgM directed against different viral antigens were measured by high-throughput automated platforms. We observed higher levels of NAbs in elderly (>60 years old) individuals and in patients presenting acute respiratory distress syndrome. SARS-CoV-2 NAbs develop as soon as five days from symptom onset and, despite a decline after the second month, persist for over 11 months, showing variable dynamics. Through correlation and receiver operating characteristic (ROC) curve analysis, we set up a testing algorithm, suitable for the laboratory workload, by establishing an optimal cutoff value of anti-SARS-CoV-2 IgG for convalescent plasma donors to exclude from MNT samples foreseen to have low/negative NAb titers and ineligible for plasma donation. Overall, MNT, although cumbersome and not suitable for routine testing of large sample sizes, remains the reference tool for the assessment of antibody-mediated immunity after SARS-CoV-2 infection. Smart testing algorithms may optimize the laboratory workflow to monitor antibody-mediated protection in COVID-19 patients, plasma donors, and vaccinated individuals.

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“…However, there is a gap in knowledge on the broad cross-protective epitopes shared between SARS-CoV-2 and SARS-CoV. Currently, findings on SARS-CoV-2 B cell epitopes mainly include the determination of antigen-antibody structural complex, bioinformatics prediction and Pepscan (26)(27)(28)(29). Undoubtedly, determination the complex structure is the most accurate method for epitope identification, but it is not readily applicable to many antigens and antibodies, for its laborious efforts with a low success rate.…”

Section: Introductionmentioning

confidence: 99%

Epitope Profiling Reveals the Critical Antigenic Determinants in SARS-CoV-2 RBD-Based Antigen

et al. 2021

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The ongoing COVID-19 pandemic caused by SARS-CoV-2 is a huge public health crisis for the globe. The receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein plays a vital role in viral infection and serves as a major target for developing neutralizing antibodies. In this study, the antibody response to the RBD of SARS-CoV-2 S protein was analyzed by a panel of sera from animals immunized with RBD-based antigens and four linear B-cell epitope peptides (R345, R405, R450 and R465) were revealed. The immunogenicity of three immunodominant peptides (R345, R405, R465) was further accessed by peptide immunization in mice, and all of them could induced potent antibody response to SARS-CoV-2 S protein, indicating that the three determinants in the RBD were immunogenic. We further generated and characterized monoclonal antibodies (15G9, 12C10 and 10D2) binding to these epitope peptides, and finely mapped the three immunodominant epitopes using the corresponding antibodies. Neutralization assays showed that all three monoclonal antibodies had neutralization activity. Results from IFA and western blotting showed that 12C10 was a cross-reactive antibody against both of SARS-CoV-2 and SARS-CoV. Results from conservative and structural analysis showed that 350VYAWN354 was a highly conserved epitope and exposed on the surface of SARS-CoV-2 S trimer, whereas 473YQAGSTP479 located in the receptor binding motif (RBM) was variable among different SARS-CoV-2 strains. 407VRQIAP412 was a highly conserved, but cryptic epitope shared between SARS-CoV-2 and SARS-CoV. These findings provide important information for understanding the humoral antibody response to the RBD of SARS-CoV-2 S protein and may facilitate further efforts to design SARS-CoV-2 vaccines and the target of COVID-19 diagnostic.

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SARS-CoV-2-induced humoral immunity through B cell epitope analysis in COVID-19 infected individuals

Cited by 32 publications

References 36 publications

Predicted B Cell Epitopes Highlight the Potential for COVID-19 to Drive Self-Reactive Immunity

Predicted B Cell Epitopes Highlight the Potential for COVID-19 to Drive Self-Reactive Immunity

SARS-CoV-2 Serum Neutralization Assay: A Traditional Tool for a Brand-New Virus

Epitope Profiling Reveals the Critical Antigenic Determinants in SARS-CoV-2 RBD-Based Antigen

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