New Paper (Other): Prediction of SARS-CoV-2 epitopes across 9360 HLA class I alleles

[kyle-dyson]

Title :Prediction of SARS-CoV-2 epitopes across 9360 HLA class I alleles

General Information

Please paste a link to the paper or a citation here:

Link: https://www.biorxiv.org/content/10.1101/2020.03.30.016931v1

What is the paper's Manubot-style citation?

Citation: @doi:10.1101/2020.03.30.016931

Is this paper primarily relevant to Background or Pathogesis?

• [ ] Background
• [ ] Pathogenesis
• [x] Methods

Please list some keywords (3-10) that help identify the relevance of this paper to COVID-19

• Epitope prediction
• pMHC
• CD8 T Cells
• Public database

Which areas of expertise are particularly relevant to the paper?

• [x] virology
• [ ] epidemiology
• [x] biostatistics
• [x] immunology
• [ ] pharmacology
• [x] other: vaccine design

Summary

Suggested questions to answer about each paper:

What did they analyze? This paper predicts high-affinity HLA class I epitopes across >9,000 HLA alleles for all 11 proteins encoded in SARS-CoV-2 proteome (144 unique peptide sequences) and made the entire data set available here: https://covid-19.parkerici.org/docs/data_sets/mhc_peptidome.html

What methods did they use? Viral sequences were obtained from the NCBI Virus resource. 9 algorithms (MHCflurry, MHCnuggetsI, NNalign, NetMHC, PickPocket, SMM, SMMPMBEC, SMMalign, NetMHC) implemented within the pVACtools software suite were used for affinity prediction.

Does this paper study COVID-19, SARS-CoV-2, or a related disease and/or virus? Yes, novel SARS-CoV-2 protein sequences were obtained from NCBI.

What is the main finding (or a few main takeaways? 6,748 unique pMHCs with predicted <500nM were found. Interestingly, this includes candidate epitopes encoded by all 11 SARS-CoV-2 proteins.

What does this paper tell us about the background and/or diagnostics/therapeutics for COVID-19 / SARS-CoV-2?

Mainly, (1) there is the potential for targeting a breadth of epitopes across all SAR-CoV-2 peptides, and (2) previously validated epitopes may bind to multiple unvalidated HLA alleles. Also, number of effective antigens across different haplotype backgrounds may correlate with the degree of protective immunity and/or pathology. Need to pair this data with outcome data from haplotyped patients to verify.

Do you have any concerns about methodology or the interpretation of these results beyond this analysis?

• Main caveat is that this is all in-silico prediction with a near guarantee of false positives and negatives.
• Affinity cuttoff of <500nM used across all all HLA alleles. It's believed that each allele independently contributes to binding affinity and thus allele-specific cutoffs might be better.
• Also this analysis is limited to class I epitopes (possibly due to the relative immaturity of class II epitope prediction algorithms).

Any comments or notes?

• Unclear to me to what degree CD8 T cells play a role in viral clearance vs contributing to disease pathology.
• What about CD4+/HLA-II class eptiope contribution to antibody responses?
• I believe spike protein is the main antigenic target for current vaccine development. This prediction finds candidate antigens across all SARS-CoV-2 proteins.

[agitter]

Thanks for adding new papers @kyle-dyson! I made a slight edit to the DOI citation, changing it to doi:10.1101/2020.03.30.016931 so it can be directly copy/pasted into the manuscript. DOI citations don't require the https://doi.org/ prefix.