Immunodominant Linear B-Cell Epitopes of SARS-CoV-2 Spike, Identified by Sera from K18-hACE2 Mice Infected with the WT or Variant Viruses

Levy, Yinon; Alcalay, Ron; Zvi, Anat; Makdasi, Efi; Peretz, Eldar; Noy-Porat, Tal; Chitlaru, Theodor; Mandelboim, Michal; Mazor, Ohad; Rosenfeld, Ronit

doi:10.3390/vaccines10020251

Cited by 5 publications

(2 citation statements)

References 47 publications

(80 reference statements)

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“…Currently (November 2023), 8,528 linear B-cell epitopes have been submitted to the Immune Epitope Database (IEDB) [44]. The majority of the methods used for linear antibody epitope discovery in SARS-CoV-2 include enzyme-linked immunosorbent assay (ELISA) [36][37][38], peptide arrays [68,69], peptide microarrays [70][71][72][73][74][75][76][77][78][79][80][81][82][83][84], phage display [43,[85][86][87][88][89][90][91][92][93], or bacterial display [94]. The top three SARS-CoV-2 source proteins of linear B cell epitopes in the IEDB data are the ORF1ab (54%), S (30%), and N (9%) proteins [44].…”

Section: Discussionmentioning

confidence: 99%

Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic

Bach,

Ghanizada,

Kirkby

et al. 2024

Preprint

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Background: Antibodies play a key role in the immune defence against infectious pathogens. Understanding the underlying process of B cell recognition is not only of fundamental interest; it supports important applications within diagnostics and therapeutics. Whereas the nature of conformational B cell epitope recognition is inherently complicated, linear B cell epitopes offer a straightforward approach that potentially can be reduced to one of peptide recognition. Methods: Using an overlapping peptide approach representing the entire proteomes of the seven main coronaviruses known to infect humans, we analysed sera pooled from eight PCR-confirmed COVID-19 convalescents and eight pre-pandemic controls. Using a high-density peptide microarray platform, 13-mer peptides overlapping by 11 amino acids were in situ synthesised and incubated with the pooled primary serum samples, followed by development with secondary fluorochrome-labelled anti-IgG and -IgA antibodies. Interactions were detected by fluorescence detection. Strong Ig interactions encompassing consecutive peptides were considered to represent "high-fidelity regions" (HFRs). These were mapped to the coronavirus proteomes using a 60% homology threshold for clustering. Results: We identified 333 human coronavirus derived HFRs. Among these, 98 (29%) mapped to SARS-CoV-2, 144 (44%) mapped to one or more of the four circulating common cold coronaviruses (CCC), and 54 (16%) cross-mapped to both SARS-CoV-2 and CCCs. The remaining 37 (11%) mapped to either SARS-CoV or MERS-CoV. Notably, the COVID-19 serum was skewed towards recognising SARS-CoV-2-mapped HFRs, whereas the pre-pandemic was skewed towards recognising CCC-mapped HFRs. In terms of absolute numbers of linear B cell epitopes, the primary targets are the ORF1ab protein (60%), the spike protein (21%), and the nucleoprotein (15%) in that order; however, in terms of epitope density, the order would be reversed. Conclusion: We identified linear B cell epitopes across coronaviruses, highlighting pan-, alpha-, beta-, or SARS-CoV-2-corona-specific B cell recognition patterns. These findings could be pivotal in deciphering past and current exposures to epidemic and endemic coronavirus. Moreover, our results suggest that pre-pandemic anti-CCC antibodies may cross-react against SARS-CoV-2, which could explain the highly variable outcome of COVID-19. Finally, the methodology used here offers a rapid and comprehensive approach to high-resolution linear B-cell epitope mapping, which could be vital for future studies of emerging infectious diseases.

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Section: Discussionmentioning

confidence: 99%

Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic

Bach,

Ghanizada,

Kirkby

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Our novel vaccine strategy, i.e., taking advantage of both the adjuvant and the tetanus toxoid in a tetanus vaccine, is different from other COVID-19 peptide vaccine strategies published in the literature, i.e., focusing on B-cell and T-cell epitope identification and adjuvant development [2] , [3] , [4] , [5] , [19] , [20] , [21] , [22] , [23] . Furthermore, we used authentic viruses in neutralization assay whereas others did not.…”

Section: Discussionmentioning

confidence: 99%

Intramuscular injection of a mixture of COVID-19 peptide vaccine and tetanus vaccine in horse induced neutralizing antibodies against authentic virus of SARS-CoV-2 Delta variant

Deng¹,

Sweeney²

2022

Vaccine: X

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Previous infection with seasonal coronaviruses does not protect male Syrian hamsters from challenge with SARS-CoV-2

Francis,

Jansen,

Yourkowski

et al. 2023

Nat Commun

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SARS-CoV-2 variants and seasonal coronaviruses continue to cause disease and coronaviruses in the animal reservoir pose a constant spillover threat. Importantly, understanding of how previous infection may influence future exposures, especially in the context of seasonal coronaviruses and SARS-CoV-2 variants, is still limited. Here we adopted a step-wise experimental approach to examine the primary immune response and subsequent immune recall toward antigenically distinct coronaviruses using male Syrian hamsters. Hamsters were initially inoculated with seasonal coronaviruses (HCoV-NL63, HCoV-229E, or HCoV-OC43), or SARS-CoV-2 pango B lineage virus, then challenged with SARS-CoV-2 pango B lineage virus, or SARS-CoV-2 variants Beta or Omicron. Although infection with seasonal coronaviruses offered little protection against SARS-CoV-2 challenge, HCoV-NL63-infected animals had an increase of the previously elicited HCoV-NL63-specific neutralizing antibodies during challenge with SARS-CoV-2. On the other hand, primary infection with HCoV-OC43 induced distinct T cell gene signatures. Gene expression profiling indicated interferon responses and germinal center reactions to be induced during more similar primary infection-challenge combinations while signatures of increased inflammation as well as suppression of the antiviral response were observed following antigenically distant viral challenges. This work characterizes and analyzes seasonal coronaviruses effect on SARS-CoV-2 secondary infection and the findings are important for pan-coronavirus vaccine design.

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Immunodominant Linear B-Cell Epitopes of SARS-CoV-2 Spike, Identified by Sera from K18-hACE2 Mice Infected with the WT or Variant Viruses

Cited by 5 publications

References 47 publications

Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic

Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic

Intramuscular injection of a mixture of COVID-19 peptide vaccine and tetanus vaccine in horse induced neutralizing antibodies against authentic virus of SARS-CoV-2 Delta variant

Previous infection with seasonal coronaviruses does not protect male Syrian hamsters from challenge with SARS-CoV-2

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