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Immunoinformatics prediction of overlapping CD8⁺ T-cell, IFN-? and IL-4 inducer CD4⁺ T-cell and linear B-cell epitopes based vaccines against COVID-19 (SARS-CoV-2).

ABSTRACT: At the beginning of the year 2020, the world was struck with a global pandemic virus referred to as SARS-CoV-2 (COVID-19) which has left hundreds of thousands of people dead. To control this virus, vaccine design becomes imperative. In this study, potential epitopes-based vaccine candidates were explored. Six hundred (600) genomes of SARS-CoV-2 were retrieved from the viPR database to generate CD8⁺ T-cell, CD4+ T-cell and linear B-cell epitopes which were screened for antigenicity, immunogenicity and non-allergenicity. The results of this study provide 19 promising candidate CD8⁺ T-cell epitopes that strongly overlap with 8 promising B-cells epitopes. Another 19 CD4⁺ T-cell epitopes were also identified that can induce IFN-? and IL-4 cytokines. The most conserved MHC-I and MHC-II for both CD8⁺ and CD4⁺ T-cell epitopes are HLA-A*02:06 and HLA-DRB1*01:01 respectively. These epitopes also bound to Toll-like receptor 3 (TLR3). The population coverage of the conserved Major Histocompatibility Complex Human Leukocyte Antigen (HLA) for both CD8⁺ T-cell and CD4⁺ T-cell ranged from 65.6% to 100%. The detailed analysis of the potential epitope-based vaccine and their mapping to the complete COVID-19 genome reveals that they are predominantly found in the location of the surface (S) and membrane (M) glycoproteins suggesting the potential involvement of these structural proteins in the immunogenic response and antigenicity of the virus. Since the majority of the potential epitopes are located on M protein, the design of multi-epitope vaccine with the structural protein is highly promising though the whole M protein could also serve as a viable epitope for the development of an attenuated vaccine. Our findings provide a baseline for the experimental design of a suitable vaccine against SARS-CoV-2.

SUBMITTER: Fatoba AJ

PROVIDER: S-EPMC7831457 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Immunoinformatics prediction of overlapping CD8+ T-cell, IFN-γ and IL-4 inducer CD4+ T-cell and linear B-cell epitopes based vaccines against COVID-19 (SARS-CoV-2).

Fatoba Abiodun J AJ Maharaj Leah L Adeleke Victoria T VT Okpeku Moses M Adeniyi Adebayo A AA Adeleke Matthew A MA

Vaccine 20210118 7

At the beginning of the year 2020, the world was struck with a global pandemic virus referred to as SARS-CoV-2 (COVID-19) which has left hundreds of thousands of people dead. To control this virus, vaccine design becomes imperative. In this study, potential epitopes-based vaccine candidates were explored. Six hundred (600) genomes of SARS-CoV-2 were retrieved from the viPR database to generate CD8+ T-cell, CD4+ T-cell and linear B-cell epitopes which were screened for antigenicity, im ...[more]

PMID: 33478794

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Project description:BackgroundRespiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause of LRTI in the elderly. The available treatments and FDA-approved vaccines for RSV only lessen the severity of the infection and are recommended for infants and elderly people.MethodsWe focused on developing a broad-spectrum vaccine that activates the immune system to directly combat RSV. The objective of this study is to identify CD4+ and CD8+ T-cell epitopes using an immunoinformatics approach to develop RSV vaccines. The efficacy of these peptides was validated through in-vitro and in-vivo studies involving healthy and diseased animal models.ResultsFor each major histocompatibility complex (MHC) class-I and II, we found three epitopes of RSV proteins including F, G, and SH with an antigenic score of >0.5 and a projected SVM score of <5. Experimental validation of these peptides on female BALB/c mice was conducted before and after infection with the RSV A2 line 19f. We found that the 3RVMHCI (CD8+) epitope of the F protein showed significant results of white blood cells (19.72 × 103 cells/μl), neutrophils (6.01 × 103 cells/μl), lymphocytes (12.98 × 103 cells/μl), IgG antibodies (36.9 µg/ml), IFN-γ (86.96 ng/L), and granzyme B (691.35 pg/ml) compared to control at the second booster dose of 10 µg. Similarly, 4RVMHCII (CD4+) of the F protein substantially induced white blood cells (27.08 × 103 cells/μl), neutrophils (6.58 × 103 cells/μl), lymphocytes (16.64 × 103 cells/μl), IgG antibodies (46.13 µg/ml), IFN-γ (96.45 ng/L), and granzyme B (675.09 pg/ml). In-vitro studies showed that 4RVMHCII produced a significant level of antibodies in sera on day 45 comparable to mice infected with the virus. 4RVMHCII also induced high IFN-γ and IL-2 secretions on the fourth day of the challenge compared to the preinfectional stage.ConclusionIn conclusion, epitopes of the F protein showed considerable immune response and are suitable for further validation.

Project description:Examining CD8+ and CD4+ T cell responses after primary Yellow Fever vaccination in a cohort of 210 volunteers, we have identified and tetramer-validated 92 CD8+ and 50 CD4+ T cell epitopes, many inducing strong and prevalent (i.e., immunodominant) T cell responses. Restricted by 40 and 14 HLA-class I and II allotypes, respectively, these responses have wide population coverage and might be of considerable academic, diagnostic and therapeutic interest. The broad coverage of epitopes and HLA overcame the otherwise confounding effects of HLA diversity and non-HLA background providing the first evidence of T cell immunodomination in humans. Also, double-staining of CD4+ T cells with tetramers representing the same HLA-binding core, albeit with different flanking regions, demonstrated an extensive diversification of the specificities of many CD4+ T cell responses. We suggest that this could reduce the risk of pathogen escape, and that multi-tetramer staining is required to reveal the true magnitude and diversity of CD4+ T cell responses. Our T cell epitope discovery approach uses a combination of (1) overlapping peptides representing the entire Yellow Fever virus proteome to search for peptides containing CD4+ and/or CD8+ T cell epitopes, (2) predictors of peptide-HLA binding to suggest epitopes and their restricting HLA allotypes, (3) generation of peptide-HLA tetramers to identify T cell epitopes, and (4) analysis of ex vivo T cell responses to validate the same. This approach is systematic, exhaustive, and can be done in any individual of any HLA haplotype. It is all-inclusive in the sense that it includes all protein antigens and peptide epitopes, and encompasses both CD4+ and CD8+ T cell epitopes. It is efficient and, importantly, reduces the false discovery rate. The unbiased nature of the T cell epitope discovery approach presented here should support the refinement of future peptide-HLA class I and II predictors and tetramer technologies, which eventually should cover all HLA class I and II isotypes. We believe that future investigations of emerging pathogens (e.g., SARS-CoV-2) should include population-wide T cell epitope discovery using blood samples from patients, convalescents and/or long-term survivors, who might all hold important information on T cell epitopes and responses.

Dataset Information

Immunoinformatics prediction of overlapping CD8⁺ T-cell, IFN-? and IL-4 inducer CD4⁺ T-cell and linear B-cell epitopes based vaccines against COVID-19 (SARS-CoV-2).

Publications

Immunoinformatics prediction of overlapping CD8<sup>+</sup> T-cell, IFN-γ and IL-4 inducer CD4<sup>+</sup> T-cell and linear B-cell epitopes based vaccines against COVID-19 (SARS-CoV-2).

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Immunoinformatics prediction of overlapping CD8+ T-cell, IFN-? and IL-4 inducer CD4+ T-cell and linear B-cell epitopes based vaccines against COVID-19 (SARS-CoV-2).

Publications

Immunoinformatics prediction of overlapping CD8<sup>+</sup> T-cell, IFN-γ and IL-4 inducer CD4<sup>+</sup> T-cell and linear B-cell epitopes based vaccines against COVID-19 (SARS-CoV-2).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Immunoinformatics prediction of overlapping CD8⁺ T-cell, IFN-? and IL-4 inducer CD4⁺ T-cell and linear B-cell epitopes based vaccines against COVID-19 (SARS-CoV-2).