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First Author:  Lu, Set al. 

Journal/preprint name: bioRxiv 

Tags: Vaccines, immunodominant epitopes 

Summary

Through stimulation of three-dimensional structures of SARS-CoV-2 Spike (S), Membrane (M), Envelope (E) and Nucleocapsid (N) proteins, Lu et al. were able to predict 33 surface-accessible epitopes; the majority of which induced antibody production in immunised mice. Immunodominant epitopes that induced neutralising antibodies mostly differed in sera of domestic (China) and European sera, which is likely the result of S/N mutations (e.g. D614G). However, as 24/33 share >80% sequence homology to SARS-CoV and bat RaTG13 strains, there is potential that such epitopes may be useful to guide pan-coronavirus vaccine development.  

Research Highlights 

  1. 33 exposed B-cell epitopes identified from stimulation of 3D structures of SARS-CoV proteins induced antibody responses against its own epitope peptide in immunised/boosted mice. 

  1. Of all epitopes, only N152-170 was immunodominant in both domestic and European samples. Gene sequencing of SARS-CoV-2 genes in both cohorts highlighted mutations between the two: D614G in S and K203R204/G189R203G204/R203G204/R203G204S344 in N. 

  1. 8 epitopes induced antibody responses in mice that could inhibit both SARS-CoV-2 D614 and G614 pseudovirus infection. A further 3 could prevent D614 infection only while 9 could inhibit G614 entry. 

  1. Most neutralising epitopes were spatially clustered near the N-terminal domain, receptor-binding domain or S2’ cleavage site. 

Impact for COVID-19 research:  

  • Majority of their findings with particular epitopes are supportive of other studies. 

  • Epitopes which can induce neutralising antibody responses to SARS-CoV-2 irrespective of mutations will be of great importance for global vaccine design, particularly as there are mutational differences between populations. 

Methodologies: 

  • Study Type: in silico, in vitro, in vivo 

  • Important cell lines/viral models used: ACE2-293T cells, D614 and G614 SARS-CoV-2 pseudoviruses 

  • Key Techniques: HBC-S-peptide VLP vaccine design, ELISA, Pseudovirus neutralisation assay, prime-boost regimen for BALB/c mice. 

Limitations: 

  • Few samples used for the domestic and imported (European) samples (n=20 total). In particular, results determining the immunodominant epitopes binding antibodies in sera have large range which may skew averages. 

  • Refer to a Table 1 in text which was not in report.