In silico identification of vaccine targets for 2019-nCoV

Abstract

The newly identified coronavirus known as 2019-nCoV has Background: posed a serious global health threat. According to the latest report (18-February-2020), it has infected more than 72,000 people globally and led to deaths of more than 1,016 people in China.The 2019 novel coronavirus proteome was aligned to a curated Methods: database of viral immunogenic peptides. The immunogenicity of detected peptides and their binding potential to HLA alleles was predicted by immunogenicity predictive models and NetMHCpan 4.0.We report identification of a comprehensive list of Results:in silico immunogenic peptides that can be used as potential targets for 2019 novel coronavirus (2019-nCoV) vaccine development. First, we found 28 nCoV peptides identical to Severe acute respiratory syndrome-related coronavirus (SARS CoV) that have previously been characterized immunogenic by T cell assays. Second, we identified 48 nCoV peptides having a high degree of similarity with immunogenic peptides deposited in The Immune Epitope Database (IEDB). Lastly, we conducted a de novo search of 2019-nCoV 9-mer peptides that i) bind to common HLA alleles in Chinese and European population and ii) have T Cell Receptor (TCR) recognition potential by positional weight matrices and a recently developed immunogenicity algorithm, iPred, and identified in total 63 peptides with a high immunogenicity potential.Given the limited time and resources to develop vaccine and Conclusions: treatments for 2019-nCoV, our work provides a shortlist of candidates for experimental validation and thus can accelerate development pipeline.

In silico identification of vaccine targets for 2019-nCoV

“…The immunogenicity of 9-mer peptides were predicted using iPred and MHC presentation scores were gauged using NetMHCpan 4.0 6 for various HLA types. In this task, we focused on haplotypes common in Chinese and European populations, which include HLA-A*02:01, HLA-A*01:01, HLA-B*07:02, HLA-B*40:01 and HLA-C*07:02 alleles (Data Table 3 4 ).…”

“…Here, we scanned all 9-mers from the 2019-nCoV proteome (9613 peptides) with Binding, Activating and Killing Position Weight Matrices (PWM, see the method section) and associated each peptide with the geometric mean of these three assays as a measure of immunogenicity (Data Table 4 4 ).…”

“…Data Table 14 ). These peptides have been shown to bind various HLA alleles, although with higher Severe acute respiratory syndrome coronavirus tendency towards HLA-A:02:01, from both class I and class II, and can be target for CD8+ and CD4+ T cells respectively.…”

Polymorphism and selection pressure of SARS-CoV-2 vaccine and diagnostic antigens: implications for immune evasion and serologic diagnostic performance

“…Predicted epitopes from these antigens (6,13) were mapped in the alignments, as well as glycosylation sites (14) to assess their conservation among viral sequences. Finally, evolutionary selection pressures on the antigens were analyzed using the Fast, Unconstrained Bayesian AppRoximation (FUBAR), as implemented in HyPhy (15) and statistical significance was considered at a threshold of P<0.1.…”

“…Most of these vaccine candidates are based on the viral S protein, or the RBD as antigen. Multiple potential vaccine epitopes have also been identified in the S as well as in the N viral proteins (6). As for diagnostics, conservation of these vaccine antigens among viral strains is critical to ensure broad protection and avoid immune evasion by the virus.…”