Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design.
Ontology highlight
ABSTRACT:
SUBMITTER: Wang D
PROVIDER: S-EPMC7563688 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Since the first outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, its high infectivity led to its prevalence around the world in an exceptionally short time. Efforts have been made to control the ongoing outbreak, and among them, vaccine developments are going on high priority. New clinical trials add to growing evidence that vaccines from many countries were highly effective at preventing SARS-CoV-2 virus infection. One of them is B cell-based vaccines, which were common during a pandemic. However, neutralizing antibody therapy becomes less effective when viruses mutate. In order to tackle the problem, we focused on T-cell immune mechanism. In this study, the mutated strains of the virus were selected globally from India (B.1.617.1 and B.1.617.2), United Kingdom (B.1.1.7), South Africa (B.1.351), and Brazil (P.1), and the overlapping peptides were collected based on mutation sites of S-protein. After that, residue scanning was used to predict the affinity between overlapping peptide and HLA-A*11:01, the most frequent human leukocyte antigen (HLA) allele among the Chinese population. Then, the binding free energy was evaluated with molecular docking to further verify the affinity changes after the mutations happen in the virus genomes. The affinity test results of three epitopes on spike protein from experimental validation were consistent with our predicted results, thereby supporting the inclusion of the epitope 374FSTFKCYGL382 in future vaccine design and providing a useful reference route to improve vaccine development.
| S-EPMC9006954 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) is an acute pneumonic disease, with no prophylactic or specific therapeutical solution. Effective and rapid countermeasure against the spread of the disease's associated virus, SARS-CoV-2, requires to incorporate the computational approach. In this study, we employed various immunoinformatics tools to design a multi-epitope vaccine polypeptide with the highest potential for activating the human immune system against SARS-CoV-2. The initial epitope set was extracted from the whole set of viral structural proteins. Potential non-toxic and non-allergenic T-cell and B-cell binding and cytokine inducing epitopes were then identified through a priori prediction. Selected epitopes were bound to each other with appropriate linkers, followed by appending a suitable adjuvant to increase the immunogenicity of the vaccine polypeptide. Molecular modelling of the 3D structure of the vaccine construct, docking, molecular dynamics simulations and free energy calculations confirmed that the vaccine peptide had high affinity for Toll-like receptor 3 binding, and that the vaccine-receptor complex was highly stable. As our vaccine polypeptide design captures the advantages of structural epitopes and simultaneously integrates precautions to avoid relevant side effects, it is suggested to be promising for elicitation of an effective and safe immune response against SARS-CoV-2 in vivo.
| S-EPMC7704662 | biostudies-literature
Project description:Through 4 June 2021, COVID-19 has caused over 172.84 million cases of infection and 3.71 million deaths worldwide. Due to its rapid dissemination and high mutation rate, it is essential to develop a vaccine harboring multiple epitopes and efficacious against multiple variants to prevent the immune escape of SARS-CoV-2. An in silico approach based on the viral genome was applied to identify 19 high-immunogenic B-cell epitopes and 499 human leukocyte antigen (HLA)-restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo-Suite and manufactured by solid-phase synthesis. Docking analysis confirmed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four peptide candidates derived from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of total IgG in serum, as well as an increase of CD19+ cells in the inguinal lymph nodes, were observed in the peptide-immunized mice compared to the control. The ratios of IFN-γ-secreting lymphocytes in CD4+ or CD8+ T-cells in the peptide-immunized mice were higher than those in the control mice. There were also a larger number of IFN-γ-secreting T-cells in the spleens of peptide-immunized mice. The peptide vaccines in this study successfully elicited antigen-specific humoral and cellular immune responses in mice. To further validate the safety and efficacy of this vaccine, animal studies using a primate model, as well as clinical trials in humans, are required.
| S-EPMC8230658 | biostudies-literature
Project description:The world has faced unprecedented disruptions like global quarantine and the COVID-19 pandemic due to SARS-CoV-2. To combat these unsettling situations, several effective vaccines have been developed and are currently being used. However, the emergence of new variants due to the high mutation rate of SARS-CoV-2 challenges the efficacy of existing vaccines and has highlighted the need for novel vaccines that will be effective against various SARS-CoV-2 variants. In this study, we exploited the four structural proteins of SARS-CoV-2 to execute a potential multi-epitope vaccine against SARS-CoV-2 and its variants. The vaccine was designed by utilizing the antigenic, non-toxic, and non-allergenic B-cell and T-cell epitopes, which were selected from conserved regions of viral proteins. To build a vaccine construct, epitopes were connected through different linkers and an adjuvant was also attached at the start of the construct to enhance the immunogenicity and specificity of the epitopes. The vaccine construct was then screened through the aforementioned filters and it scored 0.6019 against the threshold of 0.4 on VexiJen 2.0 which validates its antigenicity. Toll-like receptors (i.e., TLR2, TLR3, TLR4, TLR5, and TLR8) and vaccine construct were docked by Cluspro 2.0, and TLR8 showed strong interaction with construct having a maximum negative binding energy of - 1577.1 kCal/mole. C-IMMSIM's immune simulations over three doses of the vaccine and iMODS' molecular dynamic simulations were executed to assess the reliability of the docked complexes. The stability of the vaccine construct was evaluated through the physicochemical analyses and the findings suggested that the manufactured vaccine is stable under a wide range of circumstances and can trigger immune responses against various SARS-CoV-2 variants (due to conserved epitopes). However, to strengthen the formulation of the vaccine and assess its safety and effectiveness, additional investigations and studies are required to support the computational data of this research at in-vitro and in-vivo levels.Supplementary informationThe online version contains supplementary material available at 10.1007/s40203-023-00156-2.
| S-EPMC10374517 | biostudies-literature
Project description:A novel coronavirus (SARS-CoV-2) emerged from China in late 2019 and rapidly spread across the globe, infecting millions of people and generating societal disruption on a level not seen since the 1918 influenza pandemic. A safe and effective vaccine is desperately needed to prevent the continued spread of SARS-CoV-2; yet, rational vaccine design efforts are currently hampered by the lack of knowledge regarding viral epitopes targeted during an immune response, and the need for more in-depth knowledge on betacoronavirus immunology. To that end, we developed a computational workflow using a series of open-source algorithms and webtools to analyze the proteome of SARS-CoV-2 and identify putative T cell and B cell epitopes. Utilizing a set of stringent selection criteria to filter peptide epitopes, we identified 41 T cell epitopes (5 HLA class I, 36 HLA class II) and 6 B cell epitopes that could serve as promising targets for peptide-based vaccine development against this emerging global pathogen. To our knowledge, this is the first study to comprehensively analyze all 10 (structural, non-structural and accessory) proteins from SARS-CoV-2 using predictive algorithms to identify potential targets for vaccine development.
| S-EPMC7447814 | biostudies-literature
Project description:A novel infectious agent, SARS-CoV-2, is responsible for causing the severe respiratory disease COVID-19 and death in humans. Spike glycoprotein plays a key role in viral particles entering host cells, mediating receptor recognition and membrane fusion, and are considered useful targets for antiviral vaccine candidates. Therefore, computational techniques can be used to design a safe, antigenic, immunogenic, and stable vaccine against this pathogen. Drawing upon the structure of the S glycoprotein, we are trying to develop a potent multi-epitope subunit vaccine against SARS-CoV-2. The vaccine was designed based on cytotoxic T-lymphocyte and helper T-lymphocyte epitopes with an N-terminal adjuvant via conducting immune filters and an extensive immunoinformatic investigation. The safety and immunogenicity of the designed vaccine were further evaluated via using various physicochemical, allergenic, and antigenic characteristics. Vaccine-target (toll-like receptors: TLR2 and TLR4) interactions, binding affinities, and dynamical stabilities were inspected through molecular docking and molecular dynamic (MD) simulation methods. Moreover, MD simulations for dimeric TLRs/vaccine in the membrane-aqueous environment were performed to understand the differential domain organization of TLRs/vaccine. Further, dynamical behaviors of vaccine/TLR systems were inspected via identifying the key residues (named HUB nodes) that control interaction stability and provide a clear molecular mechanism. The obtained results from molecular docking and MD simulation revealed a strong and stable interaction between vaccine and TLRs. The vaccine's ability to stimulate the immune response was assessed by using computational immune simulation. This predicted a significant level of cytotoxic T cell and helper T cell activation, as well as IgG, interleukin 2, and interferon-gamma production. This study shows that the designed vaccine is structurally and dynamically stable and can trigger an effective immune response against viral infections.
| S-EPMC8981096 | biostudies-literature
Project description:The SARS-CoV-2 pandemic has created a public health crisis worldwide. Although vaccines against the virus are efficiently being rolled out, they are proving to be ineffective against certain emerging SARS-CoV-2 variants. The high degree of sequence similarity between SARS-CoV-2 and other human coronaviruses (HCoV) presents the opportunity for designing vaccines that may offer protection against SARS-CoV-2 and its emerging variants, with cross-protection against other HCoVs. In this study, we performed bioinformatics analyses to identify T and B cell epitopes originating from spike, membrane, nucleocapsid, and envelope protein sequences found to be evolutionarily conserved among seven major HCoVs. Evolutionary conservation of these epitopes indicates that they may have critical roles in viral fitness and are, therefore, unlikely to mutate during viral replication thus making such epitopes attractive candidates for a vaccine. Our designed vaccine construct comprises of twelve T and six B cell epitopes that are conserved among HCoVs. The vaccine is predicted to be soluble in water, stable, have a relatively long half-life, and exhibit low allergenicity and toxicity. Our docking results showed that the vaccine forms stable complex with toll-like receptor 4, while the immune simulations predicted that the vaccine may elicit strong IgG, IgM, and cytotoxic T cell responses. Therefore, from multiple perspectives, our multi-subunit vaccine design shows the potential to elicit a strong immune-protective response against SARS-CoV-2 and its emerging variants while carrying minimal risk for causing adverse effects.
| S-EPMC8310312 | biostudies-literature
Project description:The ongoing coronavirus 2019 (COVID-19) pandemic, triggered by the emerging SARS-CoV-2 virus, represents a global public health challenge. Therefore, the development of effective vaccines is an urgent need to prevent and control virus spread. One of the vaccine production strategies uses the in silico epitope prediction from the virus genome by immunoinformatic approaches, which assist in selecting candidate epitopes for in vitro and clinical trials research. This study introduces the EpiCurator workflow to predict and prioritize epitopes from SARS-CoV-2 genomes by combining a series of computational filtering tools. To validate the workflow effectiveness, SARS-CoV-2 genomes retrieved from the GISAID database were analyzed. We identified 11 epitopes in the receptor-binding domain (RBD) of Spike glycoprotein, an important antigenic determinant, not previously described in the literature or published on the Immune Epitope Database (IEDB). Interestingly, these epitopes have a combination of important properties: recognized in sequences of the current variants of concern, present high antigenicity, conservancy, and broad population coverage. The RBD epitopes were the source for a multi-epitope design to in silico validation of their immunogenic potential. The multi-epitope overall quality was computationally validated, endorsing its efficiency to trigger an effective immune response since it has stability, high antigenicity and strong interactions with Toll-Like Receptors (TLR). Taken together, the findings in the current study demonstrated the efficacy of the workflow for epitopes discovery, providing target candidates for immunogen development.
| S-EPMC8641484 | biostudies-literature
Project description:The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) urgently requires an effective vaccine for prevention. In this study, 66 epitopes containing pentapeptides of SARS-CoV-2 spike protein in the IEDB database were compared with the amino acid sequence of SARS-CoV-2 spike protein, and 66 potentially immune-related peptides of SARS-CoV-2 spike protein were obtained. Based on the single-nucleotide polymorphisms analysis of spike protein of 1218 SARS-CoV-2 isolates, 52 easily mutated sites were identified and used for vaccine epitope screening. The best vaccine candidate epitopes in the 66 peptides of SARS-CoV-2 spike protein were screened out through mutation and immunoinformatics analysis. The best candidate epitopes were connected by different linkers in silico to obtain vaccine candidate sequences. The results showed that 16 epitopes were relatively conservative, immunological, nontoxic, and nonallergenic, could induce the secretion of cytokines, and were more likely to be exposed on the surface of the spike protein. They were both B- and T-cell epitopes, and could recognize a certain number of HLA molecules and had high coverage rates in different populations. Moreover, epitopes 897-913 were predicted to have possible cross-immunoprotection for SARS-CoV and SARS-CoV-2. The results of vaccine candidate sequences screening suggested that sequences (without linker, with linker GGGSGGG, EAAAK, GPGPG, and KK, respectively) were the best. The proteins translated by these sequences were relatively stable, with a high antigenic index and good biological activity. Our study provided vaccine candidate epitopes and sequences for the research of the SARS-CoV-2 vaccine.
| S-EPMC7675516 | biostudies-literature
Project description:Genomics-led researches are engaged in tracing virus expression pattern, and induced immune responses in human to develop effective vaccine against COVID-19. In this study, targeted expression profiling and differential gene expression analysis of major histocompatibility complexes and innate immune system genes were performed through SARS-CoV-2 infected RNA-seq data of human cell line, and virus transcriptome was generated for T-and B-cell epitope prediction. Docking studies of epitopes with MHC and B-cell receptors were performed to identify potential T-and B-cell epitopes. Transcriptome analysis revealed the specific multiple allele expressions in cell line, genes for elicited induce immune response, and virus gene expression. Proposed T- and B-cell epitopes have high potential to elicit equivalent immune responses caused by SARS-CoV-2 infection which can be useful to provide links between elicited immune response and virus gene expression. This study will facilitate in vitro and in vivo vaccine related research studies in disease control.
| S-EPMC7500163 | biostudies-literature