COVID-19 Vaccine Candidates: Prediction and Validation of 174 SARS-CoV-2 Epitopes

Abstract

The recent outbreak of SARS-CoV-2 (2019-nCoV) virus has highlighted the need for fast and efficacious vaccine development. Stimulation of a proper immune response that leads to protection is highly dependent on presentation of epitopes to circulating T-cells via the HLA complex. SARS-CoV-2 is a large RNA virus and testing of all overlapping peptides in vitro to deconvolute an immune response is not feasible. Therefore HLA-binding prediction tools are often used to narrow down the number of peptides to test. We tested 19 epitope-HLA-binding prediction tools, and using an in vitro peptide MHC stability assay, we assessed 777 peptides that were predicted to be good binders across 11 MHC allotypes. In this investigation of potential SARS-CoV-2 epitopes we found that current prediction tools vary in performance when assessing binding stability, and they are highly dependent on the MHC allotype in question. Designing a COVID-19 vaccine where only a few epitope targets are included is therefore a very challenging task. Here, we present 174 SARS-CoV-2 epitopes with high prediction binding scores, validated to bind stably to 11 HLA allotypes. Our findings may contribute to the design of an efficacious vaccine against COVID-19.

Predicting the Immunogenicity of T cell epitopes: From HIV to SARS-CoV-2

“…The same analysis was performed for the 152 SARS-CoV-2 peptides identified by Prachar et al (Prachar et al, 2020), which are also verified by HLA binding assays to be strong binders to diverse HLA Class I molecules. Our classifier predicted that 98 of them are immunogenic (Table 1 and Supplementary Table S2).…”

“…Only a fraction of SARS-CoV-2 peptides that bind to HLA molecules are immunogenic Many research groups have identified peptides derived from SARS-CoV-2 that can bind with HLA molecules (Ahmed, Quadeer and McKay, 2020;Campbell et al, 2020;Grifoni et al, 2020;Nerli and Sgourakis, 2020;Prachar et al, 2020). Two different approaches were employed.…”

“…Two different approaches were employed. In one approach, peptides that bind to different HLA molecules were identified based on experimental assays (Ahmed, Quadeer and McKay, 2020;Prachar et al, 2020). In the other approach, bioinformatic tools were used to identify peptides that bind to HLA molecules (Campbell et al, 2020;Grifoni et al, 2020;Nerli and Sgourakis, 2020).…”

“…In the other approach, bioinformatic tools were used to identify peptides that bind to HLA molecules (Campbell et al, 2020;Grifoni et al, 2020;Nerli and Sgourakis, 2020). We used our trained classifier to predict the immunogenicity of peptides that were determined to bind to different HLA molecules experimentally, as reported by Ahmed et al (Ahmed, Quadeer and McKay, 2020) and Prachar et al (Prachar et al, 2020). Our classifier can be easily applied to the peptides reported by other groups too.…”

“…Moreover, these shared peptides are associated with a limited set of HLA molecules, thus providing poor coverage of the global population. Ahmed et al (Ahmed, Quadeer and McKay, 2020) and Prachar et al (Prachar et al, 2020), among other groups (Campbell et al, 2020;Nerli and Sgourakis, 2020;Prachar et al, 2020), also identified SARS-CoV-2 peptides that are capable of binding to HLA molecules, either based on MHC binding assay results or bioinformatic methods. By doing this, they identified a large pool of SARS-CoV-2 peptides that are associated with diverse HLA molecules, which cover a broad cross-section of the global population.…”