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Immunology to Immunotherapeutics of SARS-CoV-2: Identification of Immunogenic Epitopes for Vaccine Development.

ABSTRACT: The emergence of COVID19 pandemic caused by SARS-CoV-2 virus has created a global public health and socio-economic crisis. Immunoinformatics-based approaches to investigate the potential antigens is the fastest way to move towards a multiepitope-based vaccine development. This review encompasses the underlying mechanisms of pathogenesis, innate and adaptive immune signaling along with evasion pathways of SARS-CoV-2. Furthermore, it compiles the promiscuous peptides from in silico studies which are subjected to prediction of cytokine milieu using web-based servers. Out of the 434 peptides retrieved from all studies, we have identified 33 most promising T cell vaccine candidates. This review presents a list of the most potential epitopes from several proteins of the virus based on their immunogenicity, homology, conservancy and population coverage studies. These epitopes can form a basis of second generation of vaccine development as the first generation vaccines in various stages of trials mostly focus only on Spike protein. We therefore, propose them as most potential candidates which can be taken up immediately for confirmation by experimental studies.

SUBMITTER: Pandey A

PROVIDER: S-EPMC9444117 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Immunology to Immunotherapeutics of SARS-CoV-2: Identification of Immunogenic Epitopes for Vaccine Development.

Pandey Apoorva A Madan Riya R Singh Swati S

Current microbiology 20220905 10

The emergence of COVID19 pandemic caused by SARS-CoV-2 virus has created a global public health and socio-economic crisis. Immunoinformatics-based approaches to investigate the potential antigens is the fastest way to move towards a multiepitope-based vaccine development. This review encompasses the underlying mechanisms of pathogenesis, innate and adaptive immune signaling along with evasion pathways of SARS-CoV-2. Furthermore, it compiles the promiscuous peptides from in silico studies which a ...[more]

PMID: 36064873

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Project description:BackgroundThe 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.MethodsWe 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.ResultsWe 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.ConclusionsUsing 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.

Project description:BackgroundEarly in the pandemic, we designed a SARS-CoV-2 peptide vaccine containing epitope regions optimized for concurrent B cell, CD4+ T cell, and CD8+ T cell stimulation. The rationale for this design was to drive both humoral and cellular immunity with high specificity while avoiding undesired effects such as antibody-dependent enhancement (ADE).MethodsWe explored the set of computationally predicted SARS-CoV-2 HLA-I and HLA-II ligands, examining protein source, concurrent human/murine coverage, and population coverage. Beyond MHC affinity, T cell vaccine candidates were further refined by predicted immunogenicity, sequence conservation, source protein abundance, and coverage of high frequency HLA alleles. B cell epitope regions were chosen from linear epitope mapping studies of convalescent patient serum, followed by filtering for surface accessibility, sequence conservation, spatial localization near functional domains of the spike glycoprotein, and avoidance of glycosylation sites.ResultsFrom 58 initial candidates, three B cell epitope regions were identified. From 3730 (MHC-I) and 5045 (MHC-II) candidate ligands, 292 CD8+ and 284 CD4+ T cell epitopes were identified. By combining these B cell and T cell analyses, as well as a manufacturability heuristic, we proposed a set of 22 SARS-CoV-2 vaccine peptides for use in subsequent murine studies. We curated a dataset of ~ 1000 observed T cell epitopes from convalescent COVID-19 patients across eight studies, showing 8/15 recurrent epitope regions to overlap with at least one of our candidate peptides. Of the 22 candidate vaccine peptides, 16 (n = 10 T cell epitope optimized; n = 6 B cell epitope optimized) were manually selected to decrease their degree of sequence overlap and then synthesized. The immunogenicity of the synthesized vaccine peptides was validated using ELISpot and ELISA following murine vaccination. Strong T cell responses were observed in 7/10 T cell epitope optimized peptides following vaccination. Humoral responses were deficient, likely due to the unrestricted conformational space inhabited by linear vaccine peptides.ConclusionsOverall, we find our selection process and vaccine formulation to be appropriate for identifying T cell epitopes and eliciting T cell responses against those epitopes. Further studies are needed to optimize prediction and induction of B cell responses, as well as study the protective capacity of predicted T and B cell epitopes.

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Immunology to Immunotherapeutics of SARS-CoV-2: Identification of Immunogenic Epitopes for Vaccine Development.

Publications

Immunology to Immunotherapeutics of SARS-CoV-2: Identification of Immunogenic Epitopes for Vaccine Development.

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