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The rapid development and deployment of effective vaccines for the world’s population are key measures to help stop the current 2019 coronavirus disease (COVID-19) pandemic. The current pandemic was caused by a highly transmissible respiratory virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
Currently, several vaccines have received Emergency Use Authorization (EUA) from global regulatory agencies, which could protect the host against SARS-CoV-2 virus by eliciting humoral responses (antibodies ) and cellular (T cells).
In silico prediction algorithms
Various studies have used in silico Prediction algorithms to determine class I and II restricted epitopes to study SARS-CoV-2 specific T cell responses and overlapping long peptide pools (OLP). These peptides have various uses. For example, they help track responses in infected and recovering individuals, develop multi-epitope vaccines, and determine the severity of SARS-CoV-2 infection. To date, researchers have successfully identified approximately 1,500 predicted Class I epitopes for the SARS-CoV-2 virus using in silico prediction methods.
An immunogenic epitope is a peptide that is presented by auto-MHC. Typically, immunogenic peptides can trigger an immune response. The researchers said that an immunogenic SARS-CoV-2 epitope requires both empirical validations of T cell immunogenicity and direct sequencing of peptides presented by MHC. Although many of these studies determined the T cell response to these epitopes, they did not take into account their immunogenic properties. Therefore, there is a gap in the research i.e. no report is available regarding the empirical validation of SARS-CoV-2 epitopes for immunogenicity.
A new study
A new study has been published on the bioRxiv* preprint server, which used MS to identify T cell epitopes of the protein conserved by SARS-CoV-2, i.e. membrane glycol protein (MGP) and non-structural protein-13 ( NSP13). In this study, the researchers isolated peptides from MHC complexes of cells expressing SARS-CoV-2. This is the first report on the use of MS to determine T cell epitopes of virus protein. In addition, the empirical validation of the immunogenicity by in vitro synthesis of cytotoxic T lymphocytes (CTL) specific for SARS-CoV-2 was also addressed for the first time.
For this study, the authors used technology from their previous study, which involved the isolation of rare T cells reactive to peripheral blood tumors. Researchers in this study hypothesized that the immunogenic epitopes of SARS-CoV-2 can be defined empirically by analyzing peptides isolated from MHC. Subsequently, each peptide was analyzed for its ability to induce T cells against targets expressing the SARS-CoV-2 antigen.
Identification of antigenic epitopes by mass spectrometry (MS)
MS is a popular analytical tool used for the identification of naturally expressed antigenic epitopes. It helps to understand the complexity of the varied expression and processing of antigenic proteins in infected cells. Current research has identified and profiled the SARS-CoV-2 immunopeptidome by studying the immunoaffinity of the MHC-antigenic peptide complex from cells designed to express the SARS-CoV-2 genes.
The present study identified and validated five immunogenic Class I restricted epitopes from a highly conserved region of MGP and the NSP13 region of the SARS-CoV-2 genome. In this study, the researchers used recombinant vectors encoding specific alleles and engineered the expression of highly conserved regions of the SARS-CoV-2 MGP and NSP13 genes.
Thus, they recovered the MHC and eluted the peptides. Liquid chromatography-tandem mass spectrometry (DDA MS / MS) data-dependent analysis was used to analyze these peptides, which yielded over 12,000 spectra. These were deconvoluted and filtered, and five peptide epitopes were determined. The authors empirically validated cells infected with SARS-CoV-2 and the presence of these (endogenous) peptides by triggering T cell responses against these candidate epitopes.
A recent study also reported T cell responses induced by the SARS-CoV-2 vaccine, which had been linked to the elimination of the virus and its components from the host. Scientists further determined MGP65 and NSP13-specific CTLs that can identify and eliminate target cells with SARS-CoV-2 antigen.
Importance of the study
In the current scenario, the scientific community is concerned about the effectiveness of available vaccines against emerging variants of SARS-CoV-2. Indeed, all these vaccines were designed on the basis of the S protein of SARS-CoV-2, and a significant mutation in this area could lead to immune evasion. To date, none of the mutations have been found in the epitopes of the SARS-CoV-2 variants.
Therefore, the development of vaccines targeting these epitopes could be extremely effective as it will provide long-term viral immunoprotection via T cell synthesis. In addition, the epitope identification strategy is versatile, i.e. – say that the technology can identify the epitopes present in any region of the SARS-CoV2 gene.
*Important Notice
bioRxiv publishes preliminary scientific reports that are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.
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