In Silico Defined SARS-CoV2 Epitopes May Not Predict Immunogenicity to COVID19
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Abstract
SARS-CoV-2 infections elicit both humoral and cellular immune responses. For the prevention and treatment of COVID19, the disease caused by SARS-CoV-2, it has become increasingly apparent that T cell responses are equally, if not more important than humoral responses in mediating recovery and immune-protection. One of the major challenges in developing T cell-based therapies for infectious and malignant diseases has been the identification of immunogenic epitopes that can elicit a meaningful T cell response. Traditionally, this has been achieved using sophisticated in silico methods to predict putative epitopes deduced from binding affinities and consensus data. Our studies find that, in contrast to current dogma, ‘immunodominant’ SARS-CoV-2 peptides defined by such in silico methods often fail to elicit T cell responses recognizing naturally presented SARS-CoV-2 epitopes.
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SciScore for 10.1101/2021.07.08.451555: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Sorting and expansion: After two stimulation cycles, an aliquot of each well was stained with custom PE-conjugated MHC tetramer folded with HLA matched SARS-CoV2 peptide, and with APC-Cy7 conjugated anti-CD8 antibody (Biolegend, CA, USA). anti-CD8suggested: NoneExperimental Models: Cell Lines Sentences Resources TAP-deficient T-B cell hybrid cell line T2, melanoma cell line A375 ( T2suggested: NoneA375suggested: CLS Cat# 300110/p852_A-375, RRID:CVCL_0132)Melanoma cell line Mel624 … SciScore for 10.1101/2021.07.08.451555: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Sorting and expansion: After two stimulation cycles, an aliquot of each well was stained with custom PE-conjugated MHC tetramer folded with HLA matched SARS-CoV2 peptide, and with APC-Cy7 conjugated anti-CD8 antibody (Biolegend, CA, USA). anti-CD8suggested: NoneExperimental Models: Cell Lines Sentences Resources TAP-deficient T-B cell hybrid cell line T2, melanoma cell line A375 ( T2suggested: NoneA375suggested: CLS Cat# 300110/p852_A-375, RRID:CVCL_0132)Melanoma cell line Mel624 (HLA-A0201) was the gift from Dr. Steven Rosenberg (NCI) Mel624suggested: RRID:CVCL_RA32)MGP-pLVX or SP-pLVX lentiviral vector were transfected into package cell line 293T, together with package vectors contain VSVG envelop vector to make lentivirus. 293Tsuggested: CCLV Cat# CCLV-RIE 1018, RRID:CVCL_0063)A375, SK-MEL-5, and Mel624 cell lines were infected with MGP-pLVX or SP-pLVX lentiviral vectors and the stable cell lines were screened with puromycin selection. SK-MEL-5suggested: NoneRecombinant DNA Sentences Resources Lentivirus transduction: The cDNA of membrane glyco-protein (MGP) and Non-structure protein 13 (NSP13) of ORF1b from SARS-CoV-2 were purchased from Genscript (NJ, USA) and cloned into lentiviral vector pLVX (TAKARA, CA, USA) with fusion of GFP. pLVXsuggested: RRID:Addgene_101121)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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