POSSIBLE ROLE OF PEPTIDE EPITOPES OF COVID-19 BNT-162B2 MRNA VACCINE IN FOMENTING AUTOIMMUNITY: AN IN SILICO ANALYSIS

ABSTRACT

BackgroundFollowing the launch of the global COVID-19 vaccination campaign, there have been increased reports of autoimmune diseases developing de novo following vaccination. These cases include rheumatoid arthritis, autoimmune hepatitis, immune thrombotic thrombocytopenia, and connective tissue diseases. Nevertheless, COVID-19 vaccines are considered safe for patients with autoimmune diseases and are strongly recommended.ObjectivesThe aim of this in silico analysis is to investigate the presence of protein epitopes encoded by the BNT-162b2 mRNA vaccine, one of the most commonly administered COVID-19 vaccines, that could elicit an aberrant adaptive immune response in predisposed individuals.MethodsThe FASTA sequence of the protein encoded by the BNT-162b2 vaccine was retrieved from http//genome.ucsc.edu and used as a key input to the Immune Epitope Database and Analysis Resource (www.iedb.org). Linear peptides with 90% BLAST homology were selected, and T-cell, B-cell, and MHC ligand assays without MHC restriction were searched and evaluated. HLA-disease associations were screened on the HLA-SPREAD platform (https//hla-spread.igib.res.in) by selecting only positive markers.ResultsA total of 183 epitopes were found, corresponding to 178 SARS-CoV-2 and 5 SARS-CoV spike epitopes, respectively. Results were obtained from 22 T-cell assays, 398 B-cell assays, and 2 MHC ligand assays. Complementary receptors included 1080 T-cell receptors and 0 B-cell receptors.Specifically, the IEDB_epitope1329790 (NATNVVIKVCEFQFCNDPFLGVYY) was shown to bind to HLA-DRB1*1502 and HLA-DRB1*1503 alleles, whereas the IEDB_epitope1392457 (TKCTLKSFTVEKGIYQTSNFRVQPT) was reported to bind to HLA-DRB1*0701, HLA-DRB1*0301, HLA-DRB3*0101, and HLA-DRB4*0101 alleles. The HLA alleles detected were found to be positively associated with various immunological disorders (Table 1).Table 1.MHC-restricted epitopes of the BNT-162b2 vaccine and potentially associated immunological conditionsEpitopeAssayMHC moleculeAssociated disease (population)NATNVVIKVCEFQFCNDPFLGVYY + OX(C10)cellular MHC/mass spectrometry ligand presentationHLA-DRB1*1502Takayasu arteritis (Japanese) Arthritis (Taiwanese) Scleroderma (Japanese) Colitis (Japanese)HLA-DRB1*1503Systemic lupus erythematosus (Mexican American)TKCTLKSFTVEKGIYQTSNFRVQPT + SCM(K2)as aboveHLA-DRB1*0701Allergy, hypersensitivity (Caucasian)HLA-DRB1*0301Type 1 diabetes (African) Sarcoidosis, good prognosis (Finnish)HLA-DRB3*0101Graves' disease (Caucasian) Thymoma (Caucasian) Sarcoidosis (Scandinavian) Autoimmune hepatitis (Caucasian)HLA-DRB4*0101Vitiligo (Saudi Arabian)ConclusionSimilar to the SARS-CoV-2 spike protein, the protein product of the BNT-162b2 mRNA vaccine contains immunogenic epitopes that may trigger autoimmune phenomena in predisposed individuals. Genotyping for HLA alleles may help identify at-risk individuals. However, further research is needed to elucidate the underlying mechanisms and potential clinical implications.References[1]Vita R, Mahajan S, Overton JA et al. The Immune Epitope Database (IEDB) 2018 update. Nucleic Acids Res. 2019 Jan 8;47(D1)D339-D343. doi 10.1093/nar/gky1006.[2]Dholakia D, Kalra A, Misir BR et al. HLA-SPREAD a natural language processing based resource for curating HLA association from PubMed s. BMC Genomics 23, 10 (2022). https//doi.org/10.1186/s12864-021-08239-0[3]Parker R, Partridge T, Wormald C et al. Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells. Cell Rep. 2021 May 25;35(8)109179. doi 10.1016/j.celrep.2021.109179.[4]Knierman MD, Lannan MB, Spindler LJ et al. The Human Leukocyte Antigen Class II Immunopeptidome of the SARS-CoV-2 Spike Glycoprotein. Cell Rep. 2020 Dec 1;33(9)108454. doi 10.1016/j.celrep.2020.108454.AcknowledgementsNIL.Disclosure of InterestsNone Declared.