scholarly journals In silico Design of novel Multi-epitope recombinant Vaccine based on Coronavirus surface glycoprotein

2020 ◽  
Author(s):  
Mandana Behbahani
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Ribosomal Protein ◽  
In Silico ◽  
Three Dimensional ◽  
Surface Glycoprotein ◽  
Dimensional Structure ◽  
Effective Vaccine ◽  
Epitope Vaccine

AbstractIt is of special significance to find a safe and effective vaccine against coronavirus disease 2019 (COVID-19) that can induce T cell and B cell -mediated immune responses. There is currently no vaccine to prevent COVID-19. In this project, a novel multi-epitope vaccine for COVID-19 virus based on surface glycoprotein was designed through application of bioinformatics methods. At the first, seventeen potent linear B-cell and T-cell binding epitopes from surface glycoprotein were predicted in silico, then the epitopes were joined together via different linkers. The ability of the selected epitopes to induce interferon-gamma was evaluate using IFNepitope web server. One final vaccine was constructed which composed of 398 amino acids and attached to 50S ribosomal protein L7/L12 as adjuvant. Physicochemical properties, as well as antigenicity in the proposed vaccines, were checked for defining the vaccine stability and its ability to induce cell-mediated immune responses. Three-dimensional structure of the mentioned vaccine was subjected to the molecular docking studies with MHC-I and MHC-II molecules. The results proposed that the multi-epitope vaccine with 50S ribosomal protein L7/L12 was a stable construct with high aliphatic content and high antigenicity.

scholarly journals An immunoinformatics approach for the design of a multi-epitope vaccine targeting super antigen TSST-1 of Staphylococcus aureus

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Harish Babu Kolla ◽  
Chakradhar Tirumalasetty ◽  
Krupanidhi Sreerama ◽  
Vijaya Sai Ayyagari
Keyword(s):  
Staphylococcus Aureus ◽  
T Cell ◽  
B Cell ◽  
In Silico ◽  
Three Dimensional ◽  
Clinical Manifestations ◽  
Food Poisoning ◽  
Dimensional Structure ◽  
T Cell Epitopes ◽  
Epitope Vaccine

Abstract Background TSST-1 is a secretory and pyrogenic superantigen that is being responsible for staphylococcal mediated food poisoning and associated clinical manifestations. It is one of the main targets for the construction of vaccine candidates against Staphylococcus aureus. Most of the vaccines have met failure due to adverse reactions and toxicity reported during late clinical studies. To overcome this, an immunoinformatics approach is being used in the present study for the design of a multi-epitope vaccine to circumvent the problems related to toxicity and allergenicity. Results In this study, a multi-epitope vaccine against Staphylococcus aureus targeting TSST-1 was designed through an immunoinformatics approach. B cell and T cell epitopes were predicted in silico and mapped with linkers to avoid junctional immunogenicity and to ensure the efficient presentation of exposed epitopes through HLA. β-defensin and PADRE were adjusted at the N-terminal end of the final vaccine as adjuvants. Physiochemical parameters, antigenicity, and allergenicity of the vaccine construct were determined with the help of online servers. The three-dimensional structure of the vaccine protein was predicted and validated with various tools. The affinity of the vaccine with TLR-3 was studied through molecular docking studies and the interactions of two proteins were visualized using LigPlot+. The vaccine was successfully cloned in silico into pET-28a (+) for efficient expression in E. coli K12 system. Population coverage analysis had shown that the vaccine construct can cover 83.15% of the global population. Immune simulation studies showed an increase in the antibody levels, IL-2, IFN-γ, TGF-β, B cell, and T cell populations and induced primary, secondary, and tertiary immune responses. Conclusion Multi-epitope vaccine designed through a computational approach is a non-allergic and non-toxic antigen. Preliminary in silico reports have shown that this vaccine could elicit both B cell and T cell responses in the host as desired.

scholarly journals The Three-dimensional Structure of Human Splenic White Pulp Compartments

2003 ◽  
Vol 51 (5) ◽  
pp. 655-663 ◽  
Author(s):  
Birte Steiniger ◽  
Lars Rüttinger ◽  
Peter J. Barth
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
B Cell ◽  
Marginal Zone ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
White Pulp ◽  
Cell Region ◽  
Human Spleen ◽  
Splenic White Pulp

The precise arrangement of B- and T-lymphocytes in the different compartments of the human splenic white pulp is still largely unknown. We therefore performed a 3D reconstruction of 150 serial sections of a representative adult human spleen alternately stained for CD3 and CD20. The results indicate that the T-cell regions of human spleens may be interrupted by B-cell follicles. Therefore, there is no continuous periarteriolar lymphatic T-cell sheath (PALS) around white pulp arterioles. An arteriole may be surrounded by T-lymphocytes at one level, then run across a follicle without any T-cells around, and finally re-enter a T-cell region. T- and B-cell compartments are intricately interdigitated in the human splenic white pulp. CD4+ T-lymphocytes and the typical fibroblasts of the T-cell region may extend as a thin shell at the follicular surface within the marginal zone. On the other hand, IgD++ B-cells continue from the follicular outer marginal zone along the surface of the T-cell region. Our findings indicate that the microanatomy of the splenic white pulp differs between humans and rodents. This may have consequences for the immigration of recirculating lymphocytes and for initial interactions among antigen-specific T- and B-lymphocytes.

scholarly journals In Silico Characterization of Surface Glycoprotein [QHD43416] of Severe Acute Respiratory Syndrome-Coronavirus 2

2020 ◽  
Vol 3 (2) ◽  
pp. 32-36
Author(s):  
Rajneesh Prajapat ◽  
◽  
Suman Jain ◽  
Manish K Vaishnav ◽  
Sonal Sogani ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
In Silico ◽  
Three Dimensional ◽  
Surface Glycoprotein ◽  
Dimensional Structure ◽  
Model Quality ◽  
Core Section ◽  
Novel Coronavirus ◽  
And Function ◽  
Tools And Techniques

The novel coronavirus (SARS-CoV-2) reported from Wuhan, China, that spread rapidly and cause severe acute respiratory syndrome. The disease associated with infection of SARS-CoV-2 that is referred as COVID-19 (Coronavirus Disease 2019). In the present study, the surface glycoprotein [QHD43416] of SARS-CoV-2 was characterized for structure analysis and validation to provide information about its three-dimensional structure by using in silico tools and techniques. The surface glycoprotein [QHD43416] sequence of SARS-CoV-2 was retrieved from NCBI and its PDB file was designed by using phyre2 server. The RAMPAGE and UCLA-DOE (Verify 3D) was used for analysis and validation of structure model of protein. The model quality estimation based on the ProSA. Alignment of surface glycoprotein [QHD43416], revealed homology (72% identity) with spike protein of bat coronavirus [BM48-31/BGR/2008]. The model corresponding to probability conformation with 90.5% residue of core section, 9.1 % of allowed section and 0.4 % residue of outer section in φ-ψ plot, that specifies accuracy of prediction model. The Verify 3D results shows that 59.53% residues have average 3D-1D score >= 0.2 this determines compatibility of 3D model with its amino acid sequence (1D). ProSA Z-score -11.19 represents the good quality of the model. The structure and function of coronavirus surface glycoprotein could be predicted by in silico modeling studies. The protein model will be further used for designing of vaccine / drug development against coronavirus infection.

scholarly journals Immunoinformatic Approach for the identification of T Cell and B Cell Epitopes in the Surface Glycoprotein and Designing a Potent Multiepitope Vaccine Construct Against SARS-CoV-2 including the new UK variant

2021 ◽  
Author(s):  
Kaveri Krishnasamy ◽  
Gracy Fathima Selvaraj ◽  
Kiruba Ramesh ◽  
Padmaoriya Padmanabhan ◽  
Vidya Gopalan ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
T Lymphocyte ◽  
Vaccine Candidate ◽  
Surface Glycoprotein ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
New Variant

The emergence of a novel coronavirus in China in late 2019 has turned into a SARS-CoV-2 pandemic affecting several millions of people worldwide in a short span of time with high fatality. The crisis is further aggravated by the emergence and evolution of new variant SARS-CoV-2 strains in UK during December, 2020 followed by their transmission to other countries. A major concern is that prophylaxis and therapeutics are not available yet to control and prevent the virus which is spreading at an alarming rate, though several vaccine trials are in the final stage. As vaccines are developed through various strategies, their immunogenic potential may drastically vary and thus pose several challenges in offering both arms of immunity such as humoral and cell-mediated immune responses against the virus. In this study, we adopted an immunoinformatics-aided identification of B cell and T cell epitopes in the Spike protein, which is a surface glycoprotein of SARS-CoV-2, for developing a new Multiepitope vaccine construct (MEVC). MEVC has 575 amino acids and comprises adjuvants and various cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes that possess the highest affinity for the respective HLA alleles, assembled and joined by linkers. The computational data suggest that the MEVC is non-toxic, non-allergenic and thermostable with the capability to elicit both humoral and cell-mediated immune responses. The population coverage of various countries affected by COVID-19 with respect to the selected B and T cell epitopes in MEVC was also investigated. Subsequently, the biological activity of MEVC was assessed by bioinformatic tools using the interaction between the vaccine candidate and the innate immune system receptors TLR3 and TLR4. The epitopes of the construct were analyzed with that of the strains belonging to various clades including the new variant UK strain having multiple unique mutations in S protein. Due to the advantageous features, the MEVC can be tested in vitro for more practical validation and the study offers immense scope for developing a potential vaccine candidate against SARS-CoV-2 in view of the public health emergency associated with COVID-19 disease caused by SARS-CoV-2.

scholarly journals In-silico design of a multi-epitope recombinant vaccine against SARS-CoV-2 targeting the receptor binding domain

2020 ◽  
Author(s):  
Harshawardhan Pande
Keyword(s):  
T Cell ◽  
B Cell ◽  
Receptor Binding ◽  
In Silico ◽  
Neutralizing Antibodies ◽  
De Novo ◽  
Recombinant Vaccine ◽  
Binding Domain ◽  
Surface Glycoprotein ◽  
Receptor Binding Domain

The COVID-19 pandemic caused by the SARS-CoV-2 virus is posing a major global challenge due to its rapid infectivity and lethality. Despite a global effort towards creating a vaccine, no viable vaccine currently exists. While multiple bioinformatic studies have attempted to predict epitopes, they have focused on the whole spike protein without considering antibody mediated enhancement or Th-2 immunopathology and have missed some important but less antigenic epitopes in the receptor binding domain. Therefore, this study used in silico methods to design and evaluate a potential multiepitope vaccine that specifically targets the receptor binding domain due to its critical function in viral entry. Immunoinformatic tools were used to specifically examine the receptor binding domain of the surface glycoprotein for suitable T cell and B cell epitopes. The selected 5 B cell and 8 T cell epitopes were then constructed into a subunit vaccine and appropriate adjuvants along with the universal immunogenic PADRE sequence were added to boost efficacy. The structure of the vaccine construct was predicted through a de novo approach and molecular docking simulations were performed which demonstrated high affinity binding to TLR 5 receptor and appropriate HLA proteins. Finally, the vaccine candidate was cloned into an expression vector for use as a recombinant vaccine. Similarities to some recent epitope mapping studies suggest a high potential for eliciting neutralizing antibodies and generating a favorable overall immune response.

scholarly journals Conserved Regions from Neisseria gonorrhoeae Pilin Are Immunosilent and Not Immunosuppressive

2007 ◽  
Vol 75 (8) ◽  
pp. 4138-4147 ◽  
Author(s):  
Johanna K. Hansen ◽  
Karen P. Demick ◽  
John M. Mansfield ◽  
Katrina T. Forest
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Neisseria Gonorrhoeae ◽  
B Cell ◽  
Hypervariable Region ◽  
Suppressor Cell ◽  
Dimensional Structure ◽  
Cell Responses ◽  
Conserved Regions ◽  
B Cell Responses

ABSTRACT PilE is the primary subunit of type IV pili from Neisseria gonorrhoeae and contains a surface-exposed hypervariable region thought to be one feature of pili that has prevented development of a pilin-based vaccine. We have created a three-dimensional structure-based antigen by replacing the hypervariable region of PilE with an aspartate-glutamine linker chosen from the sequence of Pseudomonas aeruginosa PilA. We then characterized murine immune responses to this novel protein to determine if conserved PilE regions could serve as a vaccine candidate. The control PilE protein elicited strong T-cell-dependent B-cell responses that are specific to epitopes in both the hypervariable deletion and control proteins. In contrast, the hypervariable deletion protein was unable to elicit an immune response in mice, suggesting that in the absence of the hypervariable region, the conserved regions of PilE alone are not sufficient for antibody production. Further analysis of these PilE proteins with suppressor cell assays showed that neither suppresses T- or B-cell responses, and flow cytometry experiments suggested that they do not exert suppressor effects by activating T regulatory cells. Our results show that in the murine model, the hypervariable region of PilE is required to activate immune responses to pilin, whereas the conserved regions are unusually nonimmunogenic. In addition, we show that both hypervariable and conserved regions of pilin are not suppressive, suggesting that PilE does not cause the decrease in T-cell populations observed during gonococcal cervicitis.

scholarly journals Attenuated Subcomponent Vaccine Design Targeting the SARS-CoV-2 Nucleocapsid Phosphoprotein RNA Binding Domain: In Silico Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Onyeka S. Chukwudozie ◽  
Rebecca C. Chukwuanukwu ◽  
Onyekachi O. Iroanya ◽  
Daniel M. Eze ◽  
Vincent C. Duru ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
In Silico ◽  
Rna Binding ◽  
Peptide Vaccine ◽  
In Silico Analysis ◽  
Dynamics Simulation ◽  
Effective Vaccine ◽  
Translation Efficiency ◽  
T Cell Epitopes

The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has previously never been identified with humans, thereby creating devastation in public health. The need for an effective vaccine to curb this pandemic cannot be overemphasized. In view of this, we designed a subcomponent antigenic peptide vaccine targeting the N-terminal (NT) and C-terminal (CT) RNA binding domains of the nucleocapsid protein that aid in viral replication. Promising antigenic B cell and T cell epitopes were predicted using computational pipelines. The peptides “RIRGGDGKMKDL” and “AFGRRGPEQTQGNFG” were the B cell linear epitopes with good antigenic index and nonallergenic property. Two CD8+ and Three CD4+ T cell epitopes were also selected considering their safe immunogenic profiling such as allergenicity, antigen level conservancy, antigenicity, peptide toxicity, and putative restrictions to a number of MHC-I and MHC-II alleles. With these selected epitopes, a nonallergenic chimeric peptide vaccine incapable of inducing a type II hypersensitivity reaction was constructed. The molecular interaction between the Toll-like receptor-5 (TLR5) which was triggered by the vaccine was analyzed by molecular docking and scrutinized using dynamics simulation. Finally, in silico cloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing the pET-28a vector. This research, therefore, provides a guide for experimental investigation and validation.

scholarly journals In Silico screening of T-cell and B-cell Epitopes of Rotavirus VP7 and VP4 proteins for Effective Vaccine Design

2019 ◽  
Vol 35 (1) ◽  
pp. 45-55
Author(s):  
Md Sadikur Rahman Shuvo ◽  
Sanjoy Kumar Mukharjee ◽  
Firoz Ahmed
Keyword(s):  
Developing Countries ◽  
T Cell ◽  
B Cell ◽  
In Silico ◽  
Child Death ◽  
Vaccine Design ◽  
Effective Vaccine ◽  
World Population ◽  
Promising Alternative ◽  
B Cell Epitopes

Rotavirus is one of the deadliest causative agents of childhood diarrhea which causes half a million child death across the globe, mostly in developing countries. However, effective vaccine strategies against rotavirus are yet to be established to prevent these unwanted premature deaths. In this regard, in silico vaccine design for rotavirus could be a promising alternative for developing countries due to its efficiency in shortening valuable time and cost. The present study described an epitope-based peptide vaccine design against rotavirus, using a combination of T-cell and B-cell epitope predictions and molecular docking approach. To perform this, sequences of rotavirus VP7 and VP4 proteins were retrieved from the NCBI database and subjected to different bioinformatics tools to predict most immunogenic T-cell and B-cell epitopes. From the identified epitopes, the sequence VMSKRSRSL of VP7 and TQFTDFVSL of VP4 was identified as the most potential epitopes based on their antigenicity, conservancy and interaction with major histocompatability complex I (MHC-I) alleles. Moreover, the peptide VMSKRSRSL interacted with human leukocyte antigen, HLA-B*08:01 and TQFTDFVSL interacted with HLA-A*02:06 with considerable binding energy and affinity score. Combined population coverage for our identified epitopes was found 70.53% and 45.64% for world population and South Asian population respectively. All these results suggest that, the epitopes identified in this study could be a very good vaccine candidate for the strains of rotavirus circulating in Bangladesh. However, as this study is completely dependent on computational prediction algorithms, further in vivo screening is required to come up in a precise conclusion about these epitopes for effective rotavirus vaccination. Bangladesh J Microbiol, Volume 35 Number 1 June 2018, pp 45-55

scholarly journals Integrated Core Proteomics, Subtractive Proteomics, and Immunoinformatics Investigation to Unveil a Potential Multi-Epitope Vaccine against Schistosomiasis

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 658
Author(s):  
Abdur Rehman ◽  
Sajjad Ahmad ◽  
Farah Shahid ◽  
Aqel Albutti ◽  
Ameen S. S. Alwashmi ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Calcium Binding ◽  
Parasitic Infection ◽  
Cytotoxic T Cell ◽  
Effective Vaccine ◽  
Epitope Vaccine ◽  
Mhc Molecules ◽  
Antigenic Proteins ◽  
Subtractive Proteomics

Schistosomiasis is a parasitic infection that causes considerable morbidity and mortality in the world. Infections of parasitic blood flukes, known as schistosomes, cause the disease. No vaccine is available yet and thus there is a need to design an effective vaccine against schistosomiasis. Schistosoma japonicum, Schistosoma mansoni, and Schistosoma haematobium are the main pathogenic species that infect humans. In this research, core proteomics was combined with a subtractive proteomics pipeline to identify suitable antigenic proteins for the construction of a multi-epitope vaccine (MEV) against human-infecting Schistosoma species. The pipeline revealed two antigenic proteins—calcium binding and mycosubtilin synthase subunit C—as promising vaccine targets. T and B cell epitopes from the targeted proteins were predicted using multiple bioinformatics and immunoinformatics databases. Seven cytotoxic T cell lymphocytes (CTL), three helper T cell lymphocytes (HTL), and four linear B cell lymphocytes (LBL) epitopes were fused with a suitable adjuvant and linkers to design a 217 amino-acid-long MEV. The vaccine was coupled with a TLR-4 agonist (RS-09; Sequence: APPHALS) adjuvant to enhance the immune responses. The designed MEV was stable, highly antigenic, and non-allergenic to human use. Molecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized Born surface area (MMGBSA) analysis were performed to study the binding affinity and molecular interactions of the MEV with human immune receptors (TLR2 and TLR4) and MHC molecules (MHC I and MHC II). The MEV expression capability was tested in an Escherichia coli (strain-K12) plasmid vector pET-28a(+). Findings of these computer assays proved the MEV as highly promising in establishing protective immunity against the pathogens; nevertheless, additional validation by in vivo and in vitro experiments is required to discuss its real immune-protective efficacy.

In Silico Prediction of Epitopes in Virulence Proteins of Mycobacterium ulcerans for Vaccine Designing

2021 ◽  
Vol 22 ◽  
Author(s):  
Taruna Mohinani ◽  
Aditya Saxena ◽  
Shoor Vir Singh
Keyword(s):  
T Cell ◽  
B Cell ◽  
In Silico ◽  
Three Dimensional ◽  
Cell Epitope ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
T Cell Epitopes ◽  
Virulence Proteins ◽  
Vaccine Potential

Background: Mycobacterium ulcerans is the fundamental agent of the third most common Mycobacterial disease known as Buruli Ulcer (BU). It is an infection of the skin and soft tissue affecting the human population worldwide. Presently, the vaccine is not available against BU. Objective: This study aimed to investigate the vaccine potential of virulence proteins of M. ulcerans computationally. Methods: Chromosome encoded virulence proteins of Mycobacterium ulcerans strain Agy99 were selected, which were available at the VFDB database. These proteins were analyzed for their subcellular localization, antigenicity, and human non-homology analysis. Ten virulence factors were finally chosen and analyzed for further study. Three-dimensional structures for selected proteins were predicted using Phyre2. B cell and T cell epitope analysis was done using methods available at Immune Epitope Database and Analysis Resource. Antigenicity, allergenicity, and toxicity analysis were also done to predict epitopes. Molecular docking analysis was done for T cell epitopes, those showing overlap with B cell epitopes. Results: Selected virulence proteins were predicted with B cell and T cell epitopes. Some of the selected proteins were found to be already reported as antigenic in other mycobacteria. Some of the predicted epitopes also had similarities with experimentally identified epitopes of M. ulcerans and M. tuberculosis which further supported our predictions. Conclusion : In-silico approach used for the vaccine candidate identification predicted some virulence proteins that could be proved important in future vaccination strategies against this chronic disease. Predicted epitopes require further experimental validation for their potential use as peptide vaccines.

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