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10.1186/s13073-020-00767-w

http://scihub22266oqcxt.onion/10.1186/s13073-020-00767-w
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32791978!7425796!32791978
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suck abstract from ncbi


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pmid32791978      Genome+Med 2020 ; 12 (1): 70
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  • Sequence-based prediction of SARS-CoV-2 vaccine targets using a mass spectrometry-based bioinformatics predictor identifies immunogenic T cell epitopes #MMPMID32791978
  • Poran A; Harjanto D; Malloy M; Arieta CM; Rothenberg DA; Lenkala D; van Buuren MM; Addona TA; Rooney MS; Srinivasan L; Gaynor RB
  • Genome Med 2020[Aug]; 12 (1): 70 PMID32791978show ga
  • BACKGROUND: The ongoing COVID-19 pandemic has created an urgency to identify novel vaccine targets for protective immunity against SARS-CoV-2. Early reports identify protective roles for both humoral and cell-mediated immunity for SARS-CoV-2. METHODS: We leveraged our bioinformatics binding prediction tools for human leukocyte antigen (HLA)-I and HLA-II alleles that were developed using mass spectrometry-based profiling of individual HLA-I and HLA-II alleles to predict peptide binding to diverse allele sets. We applied these binding predictors to viral genomes from the Coronaviridae family and specifically focused on T cell epitopes from SARS-CoV-2 proteins. We assayed a subset of these epitopes in a T cell induction assay for their ability to elicit CD8(+) T cell responses. RESULTS: We first validated HLA-I and HLA-II predictions on Coronaviridae family epitopes deposited in the Virus Pathogen Database and Analysis Resource (ViPR) database. We then utilized our HLA-I and HLA-II predictors to identify 11,897 HLA-I and 8046 HLA-II candidate peptides which were highly ranked for binding across 13 open reading frames (ORFs) of SARS-CoV-2. These peptides are predicted to provide over 99% allele coverage for the US, European, and Asian populations. From our SARS-CoV-2-predicted peptide-HLA-I allele pairs, 374 pairs identically matched what was previously reported in the ViPR database, originating from other coronaviruses with identical sequences. Of these pairs, 333 (89%) had a positive HLA binding assay result, reinforcing the validity of our predictions. We then demonstrated that a subset of these highly predicted epitopes were immunogenic based on their recognition by specific CD8(+) T cells in healthy human donor peripheral blood mononuclear cells (PBMCs). Finally, we characterized the expression of SARS-CoV-2 proteins in virally infected cells to prioritize those which could be potential targets for T cell immunity. CONCLUSIONS: Using our bioinformatics platform, we identify multiple putative epitopes that are potential targets for CD4(+) and CD8(+) T cells, whose HLA binding properties cover nearly the entire population. We also confirm that our binding predictors can predict epitopes eliciting CD8(+) T cell responses from multiple SARS-CoV-2 proteins. Protein expression and population HLA allele coverage, combined with the ability to identify T cell epitopes, should be considered in SARS-CoV-2 vaccine design strategies and immune monitoring.
  • |Alleles[MESH]
  • |Antibody Affinity[MESH]
  • |COVID-19[MESH]
  • |COVID-19 Vaccines[MESH]
  • |Computational Biology[MESH]
  • |Coronavirus Infections/genetics/*immunology/prevention & control[MESH]
  • |Epitopes/chemistry/genetics/*immunology[MESH]
  • |Genome, Viral[MESH]
  • |HLA Antigens/chemistry/genetics/*immunology[MESH]
  • |Humans[MESH]
  • |Immunogenicity, Vaccine[MESH]
  • |Mass Spectrometry[MESH]
  • |Pandemics[MESH]
  • |Pneumonia, Viral/*immunology[MESH]
  • |T-Lymphocytes/*immunology[MESH]


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