Review of Immunoinformatic approaches to in-silico B-cell epitope prediction

In this paper, the current state of in-silico, B-cell epitope prediction is discussed. Recommendations for improving some of the approaches encountered are outlined, along with the presentation of an entirely novel technique, which uses molecular mechanics for epitope classification, evaluation and prediction

Predicting Candidate Epitopes on Ebola Virus for Possible Vaccine Development

Zaire ebolavirus, a member of family Filoviridae is the cause of hemorrhagic fever. Due to lack of appropriate antiviral or vaccine, this disease is very lethal. In this study, we tried to find epitopes for superficial glycoprotein and nucleoprotein of Zaire ebolavirus (that have high antigenicity for MHC I, II and B cells) by using in silico methods and immunoinformatics approach. By using CTLPred, SYFPEITHI and ProPred web applications for MHC class I and SYFPEITHI and ProPred1 web applications for MHC class II, we had been able to find epitopes (peptides) that have the highest score. Also ElliPro, IgPred and DiscoTope web tools had been performed to predict B cells conformational epitopes. Linear epitope prediction for B cell was performed with six methods from IEDB. All of the results that including candidate epitopes for T cells and B cells were reported. It was expected that these peptides could be stimulated immune response and used for designing the multipeptide vaccine against ZEV but these results should be reliable with experimental analysis

Biomarkers of Immunotoxicity for Environmental and Public Health Research

The immune response plays an important role in the pathophysiology of numerous diseases including asthma, autoimmunity and cancer. Application of biomarkers of immunotoxicity in epidemiology studies and human clinical trials can improve our understanding of the mechanisms that underlie the associations between environmental exposures and development of these immune-mediated diseases. Immunological biomarkers currently used in environmental health studies include detection of key components of innate and adaptive immunity (e.g., complement, immunoglobulin and cell subsets) as well as functional responses and activation of key immune cells. The use of high-throughput assays, including flow cytometry, Luminex, and Multi-spot cytokine detection methods can further provide quantitative analysis of immune effects. Due to the complexity and redundancy of the immune response, an integrated assessment of several components of the immune responses is needed. The rapidly expanding field of immunoinformatics will also aid in the synthesis of the vast amount of data being generated. This review discusses and provides examples of how the identification and development of immunological biomarkers for use in studies of environmental exposures and immune-mediated disorders can be achieved

Time for T? Immunoinformatics Addresses Vaccine Design for Neglected Tropical and Emerging Infectious Diseases

Vaccines have been invaluable for global health, saving lives and reducing healthcare costs, while also raising the quality of human life. However, newly emerging infectious diseases (EID) and more well-established tropical disease pathogens present complex challenges to vaccine developers; in particular, neglected tropical diseases, which are most prevalent among the world\u27s poorest, include many pathogens with large sizes, multistage life cycles and a variety of nonhuman vectors. EID such as MERS-CoV and H7N9 are highly pathogenic for humans. For many of these pathogens, while their genomes are available, immune correlates of protection are currently unknown. These complexities make developing vaccines for EID and neglected tropical diseases all the more difficult. In this review, we describe the implementation of an immunoinformatics-driven approach to systematically search for key determinants of immunity in newly available genome sequence data and design vaccines. This approach holds promise for the development of 21st century vaccines, improving human health everywhere

Controlling Influenza by Cytotoxic T-Cells: Calling for Help from Destroyers

Influenza is a vaccine preventable disease that causes severe illness and excess mortality in humans. Licensed influenza vaccines induce humoral immunity and protect against strains that antigenically match the major antigenic components of the vaccine, but much less against antigenically diverse influenza strains. A vaccine that protects against different influenza viruses belonging to the same subtype or even against viruses belonging to more than one subtype would be a major advance in our battle against influenza. Heterosubtypic immunity could be obtained by cytotoxic T-cell (CTL) responses against conserved influenza virus epitopes. The molecular mechanisms involved in inducing protective CTL responses are discussed here. We also focus on CTL vaccine design and point to the importance of immune-related databases and immunoinformatics tools in the quest for new vaccine candidates. Some techniques for analysis of T-cell responses are also highlighted, as they allow estimation of cellular immune responses induced by vaccine preparations and can provide correlates of protection

Predicting Multi-Epitope Peptide Cancer Vaccine from Novel TAA Topo48

Cancer is one of the most lethal diseases. Recently, cancer immunotherapy has a tremendous achievement in cancer treatment. A certain number of cancer based epitope vaccines with different moiety have been discovered. In japan, several clinical tests of cancer based epitope vaccine derived from tumor associated antigens (TAAs) are now ongoing or have recently been completed. a novel of TAAs potentially as cancer vaccine have been retrieved from a fragment weighed 48kDa derived from human DNA-topoisomerase 1 (TOP1) called Topo48. Therefore, it is still critical to discover a derived Topo48 epitope based cancer vaccine. Immuno-informatics considered as a methods noted to have better accuracy to design promising vaccine candidates. Here, continuous and discontinuous B-cell epitopes following with CTL epitopes and their docking interaction to major histocompatibility complex (MHC) class I Human Leukocyte Antigens (HLA)- A0201 were predicted. Kolaskar-Tongaonkar’s, Emini’s, Karpus-Schulz’s, and Parker’s methods were used to predict continuous B-cell epitopes while ElliPro was used for prediction of discontinued B-cell epitopes. Those considered methods marked to have better accuracy to design promising vaccine candidates.  Similarly, CTL epitopes was also predicted by using NetCTL server and the best candidates were further investigated their binding affinity by mean of PEP-FOLD3, PatchDock rigid-body docking server, and FireDock server. Total 27 continuous epitopes and 7 discontinuous B-cell epitopes were predicted. In the other hand, 9 peptides were predicted as CTL epitopes. Whereas, three predicted CTL epitope in range 263MLDHEYTTK27, 755AIDMADEDY763, 715ALGTSKLNY724) exhibited good interactions to HLA-A0201. Moreover, we also found residues His266, Thr270, Ala755, Tyr723, Thr718, Ser719, Lys720 from Topo48 and residues Thr163, Asp757, His70, Glu63 from HLA- A0201 were indicated to be antigenic. Ultimately, our proposed continuous/discontinuous B-cell epitopes, and also CTL epitopes can be potential vaccines for cancer immunotherapy

An overview of bioinformatics tools for epitope prediction: Implications on vaccine development

AbstractExploitation of recombinant DNA and sequencing technologies has led to a new concept in vaccination in which isolated epitopes, capable of stimulating a specific immune response, have been identified and used to achieve advanced vaccine formulations; replacing those constituted by whole pathogen-formulations. In this context, bioinformatics approaches play a critical role on analyzing multiple genomes to select the protective epitopes in silico. It is conceived that cocktails of defined epitopes or chimeric protein arrangements, including the target epitopes, may provide a rationale design capable to elicit convenient humoral or cellular immune responses. This review presents a comprehensive compilation of the most advantageous online immunological software and searchable, in order to facilitate the design and development of vaccines. An outlook on how these tools are supporting vaccine development is presented. HIV and influenza have been taken as examples of promising developments on vaccination against hypervariable viruses. Perspectives in this field are also envisioned

T-cell epitope prediction and immune complex simulation using molecular dynamics: state of the art and persisting challenges

Atomistic Molecular Dynamics provides powerful and flexible tools for the prediction and analysis of molecular and macromolecular systems. Specifically, it provides a means by which we can measure theoretically that which cannot be measured experimentally: the dynamic time-evolution of complex systems comprising atoms and molecules. It is particularly suitable for the simulation and analysis of the otherwise inaccessible details of MHC-peptide interaction and, on a larger scale, the simulation of the immune synapse. Progress has been relatively tentative yet the emergence of truly high-performance computing and the development of coarse-grained simulation now offers us the hope of accurately predicting thermodynamic parameters and of simulating not merely a handful of proteins but larger, longer simulations comprising thousands of protein molecules and the cellular scale structures they form. We exemplify this within the context of immunoinformatics