Immunoinformatics and molecular dynamics approaches: Next generation vaccine design against West Nile virus

Khan, Md. Tahsin; Islam, Rahatul; Jerin, Tarhima Jahan; Mahmud, Araf; Khatun, Soyema; Kobir, Ahasanul; Islam, Nahidul; Akter, Arzuba; Mondal, Shakhinur Islam

doi:10.1371/journal.pone.0253393

Cited by 28 publications

(14 citation statements)

References 141 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MD simulation is an effective method for the analysis of biological systems and it provides many mechanistic insights into the possible behavior of the system under a simulated biological environment [121]. Gromacs 2020.4 was used to carry out the production phase MD and the analysis of resulting trajectories was undertaken to understand the structural properties, and interaction between different TLRs and the predicted vaccine protein at a molecular level.…”

Section: Resultsmentioning

confidence: 99%

Exploring different virulent proteins of human respiratory syncytial virus for designing a novel epitope-based polyvalent vaccine: Immunoinformatics and molecular dynamics approaches

Moin

Ullah

Patil

et al. 2022

Preprint

View full text Add to dashboard Cite

Human Respiratory Syncytial Virus (RSV) is one of the most prominent causes of lower respiratory tract infections (LRTI), contributory to infecting people from all age groups - a majority of which comprises infants and children. The implicated severe RSV infections lead to numerous deaths of multitudes of the overall population, predominantly the children, every year. Consequently, despite several distinctive efforts to develop a vaccine against the RSV as a potential countermeasure, there is no approved or licensed vaccine available yet, to control the RSV infection effectively. Therefore, through the utilization of immunoinformatics tools, a computational approach was taken in this study, to design and construct a multi-epitope polyvalent vaccine against the RSV-A and RSV-B strains of the virus. Potential predictions of the T-cell and B-cell epitopes were followed by extensive tests of antigenicity, allergenicity, toxicity, conservancy, homology to human proteome, transmembrane topology, and cytokine-inducing ability. The most promising epitopes (i.e. 13 CTL epitopes, 9 HTL epitopes, and 10 LBL epitopes) exhibiting full conservancy were then selected for designing the peptide fusion with appropriate linkers, having hBD-3 as the adjuvant. The peptide vaccine was modeled, refined, and validated to further improve the structural attributes. Following this, molecular docking analysis with specific TLRs was carried out which revealed excellent interactions and global binding energies. Additionally, molecular dynamics (MD) simulation was conducted which ensured the stability of the interactions between vaccine and TLR. Furthermore, mechanistic approaches to imitate and predict the potential immune response generated by the administration of vaccines were determined through immune simulations. Owing to an overall evaluation, in silico cloning was carried out in efforts to generate recombinant pETite plasmid vectors for subsequent mass production of the vaccine peptide, incorporated within E.coli . However, more in vitro and in vivo experiments can further validate its efficacy against RSV infections.

show abstract

Section: Resultsmentioning

confidence: 99%

Exploring different virulent proteins of human respiratory syncytial virus for designing a novel epitope-based polyvalent vaccine: Immunoinformatics and molecular dynamics approaches

Moin

Ullah

Patil

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…All selected epitopes in the vaccine construct that met the scrutiny were used to build up the vaccine. A robust immune response necessitates the use of an adjuvant which hones the antigens visibility to identifiable immune response using a proven RS 09 adjuvant ([ 74 ], and attaching an adjuvant to a vaccine necessitates the use of a linker, resulting in the entire vaccine design, and between two epitopes, linkers such as EAAAK, AAY and GPGPG are inserted to achieve the effective separation required for the epitope's effectiveness; these linkers functions differently for rigidity and plasticity in effective vaccine construct [61, [ 75 ]. EAAAK linker is a rigid α-helix forming peptide, with intramolecular hydrogen bonding having a closed packed backbone.…”

Section: Discussionmentioning

confidence: 99%

Computational construction of a glycoprotein multi-epitope subunit vaccine candidate for old and new South-African SARS-CoV-2 virus strains

Oluwagbemi

Oladipo

Dairo

et al. 2022

Informatics in Medicine Unlocked

View full text Add to dashboard Cite

The discovery of a new SARS-CoV-2 virus strain in South Africa presents a major public health threat, therefore contributing to increased infections and transmission rates during the second wave of the global pandemic. This study lays the groundwork for the development of a novel subunit vaccine candidate from the circulating strains of South African SARS-CoV-2 and provides an understanding of the molecular epidemiological trend of the circulating strains. A total of 475 whole-genome nucleotide sequences from South Africa submitted between December 1, 2020 and February 15, 2021 available at the GISAID database were retrieved based on its size, coverage level and hosts. To obtain the distribution of the clades and lineages of South African SARS-CoV-2 circulating strains, the metadata of the sequence retrieved were subjected to an epidemiological analysis. There was a prediction of the cytotoxic T lymphocytes (CTL), Helper T cells (HTL) and B-cell epitopes. Furthermore, there was allergenicity, antigenicity and toxicity predictions on the epitopes. The analysis of the physicochemical properties of the vaccine construct was performed; the secondary structure, tertiary structure and B-cell 3D conformational structure of the vaccine construct were predicted. Also, molecular binding simulations and dynamics simulations were adopted in the prediction of the vaccine construct's stability and binding affinity with TLRs. Result obtained from the metadata analysis indicated lineage B.1.351 to be in higher circulation among various circulating strains of SARS-CoV-2 in South Africa and GH has the highest number of circulating clades. The construct of the novel vaccine was antigenic, non-allergenic and non-toxic. The Instability index (II) score and aliphatic index were estimated as 41.74 and 78.72 respectively. The computed half-life in mammalian reticulocytes was 4.4 h in vitro, for yeast and in E. coli was >20 h and >10 h in vivo respectively. The grand average of hydropathicity (GRAVY) score is estimated to be −0.129, signifying the hydrophilic nature of the protein. The molecular docking indicates that the vaccine construct has a high binding affinity towards the TLRs with TLR 3 having the highest binding energy (−1203.2 kcal/mol) and TLR 9 with the lowest (−1559.5 kcal/mol). These results show that the vaccine construct is promising and should be evaluated using animal model.

show abstract

“…The PADRE peptide induces CD4+ T-cells that increase efficacy and potency of peptide vaccine ( 135 ). It also overcomes the problems caused by highly polymorphic HLA alleles ( 88 ). Linkers ensure effective separation of individual epitopes in vivo ( 136 ).…”

Section: Discussionmentioning

confidence: 99%

“…The most B-cell epitopes are discontinuous epitopes composed of amino acid residues located on separate regions of the protein, joined together by the folding of the chain ( 143 ). Thus, analysis of discontinuous epitope in the final vaccine construct is essential ( 88 ).…”

Section: Discussionmentioning

confidence: 99%

“…3Drefine server is based in optimization of the hydrogen bonding network and composite physics and knowledge-based force fields to give atomic-level energy minimization using the MESHI molecular modeling framework ( 85 , 86 ). The validation process was performed using the PROCHECK’s Ramachandran plot analysis ( ) ( 87 ) that analyzes the geometry of the refined vaccine construct and predict the best stereochemical quality of the construct ( 88 ); ProSA ( ) ( 89 ) that computes the overall quality score (Z score) for a specific 3D structure ( 90 ); and ERRAT server ( ) ( 91 ) that analyzes the statistics of non-bonded interactions between different atom types ( 92 ).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

A Systematic Immuno-Informatic Approach to Design a Multiepitope-Based Vaccine Against Emerging Multiple Drug Resistant Serratia marcescens

et al. 2022

View full text Add to dashboard Cite

Serratia marcescens is now an important opportunistic pathogen that can cause serious infections in hospitalized or immunocompromised patients. Here, we used extensive bioinformatic analyses based on reverse vaccinology and subtractive proteomics-based approach to predict potential vaccine candidates against S. marcescens. We analyzed the complete proteome sequence of 49 isolate of Serratia marcescens and identified 5 that were conserved proteins, non-homologous from human and gut flora, extracellular or exported to the outer membrane, and antigenic. The identified proteins were used to select 5 CTL, 12 HTL, and 12 BCL epitopes antigenic, non-allergenic, conserved, hydrophilic, and non-toxic. In addition, HTL epitopes were able to induce interferon-gamma immune response. The selected peptides were used to design 4 multi-epitope vaccines constructs (SMV1, SMV2, SMV3 and SMV4) with immune-modulating adjuvants, PADRE sequence, and linkers. Peptide cleavage analysis showed that antigen vaccines are processed and presented via of MHC class molecule. Several physiochemical and immunological analyses revealed that all multiepitope vaccines were non-allergenic, stable, hydrophilic, and soluble and induced the immunity with high antigenicity. The secondary structure analysis revealed the designed vaccines contain mainly coil structure and alpha helix structures. 3D analyses showed high-quality structure. Molecular docking analyses revealed SMV4 as the best vaccine construct among the four constructed vaccines, demonstrating high affinity with the immune receptor. Molecular dynamics simulation confirmed the low deformability and stability of the vaccine candidate. Discontinuous epitope residues analyses of SMV4 revealed that they are flexible and can interact with antibodies. In silico immune simulation indicated that the designed SMV4 vaccine triggers an effective immune response. In silico codon optimization and cloning in expression vector indicate that SMV4 vaccine can be efficiently expressed in E. coli system. Overall, we showed that SMV4 multi-epitope vaccine successfully elicited antigen-specific humoral and cellular immune responses and may be a potential vaccine candidate against S. marcescens. Further experimental validations could confirm its exact efficacy, the safety and immunogenicity profile. Our findings bring a valuable addition to the development of new strategies to prevent and control the spread of multidrug-resistant Gram-negative bacteria with high clinical relevance.

show abstract

Immunoinformatics and molecular dynamics approaches: Next generation vaccine design against West Nile virus

Cited by 28 publications

References 141 publications

Exploring different virulent proteins of human respiratory syncytial virus for designing a novel epitope-based polyvalent vaccine: Immunoinformatics and molecular dynamics approaches

Exploring different virulent proteins of human respiratory syncytial virus for designing a novel epitope-based polyvalent vaccine: Immunoinformatics and molecular dynamics approaches

Computational construction of a glycoprotein multi-epitope subunit vaccine candidate for old and new South-African SARS-CoV-2 virus strains

A Systematic Immuno-Informatic Approach to Design a Multiepitope-Based Vaccine Against Emerging Multiple Drug Resistant Serratia marcescens

Contact Info

Product

Resources

About