Development of an epitope conservancy analysis tool to facilitate the design of epitope-based diagnostics and vaccines

<p>Abstract</p> <p>Background</p> <p>In an epitope-based vaccine setting, the use of conserved epitopes would be expected to provide broader protection across multiple strains, or even species, than epitopes derived from highly variable genome regions. Conversely, in a diagnostic and disease monitoring setting, epitopes that are specific to a given pathogen strain, for example, can be used to monitor responses to that particular infectious strain. In both cases, concrete information pertaining to the degree of conservancy of the epitope(s) considered is crucial.</p> <p>Results</p> <p>To assist in the selection of epitopes with the desired degree of conservation, we have developed a new tool to determine the variability of epitopes within a given set of protein sequences. The tool was implemented as a component of the Immune Epitope Database and Analysis Resources (IEDB), and is directly accessible at <url>http://tools.immuneepitope.org/tools/conservancy</url>.</p> <p>Conclusion</p> <p>An epitope conservancy analysis tool was developed to analyze the variability or conservation of epitopes. The tool is user friendly, and is expected to aid in the design of epitope-based vaccines and diagnostics.</p

Predicting population coverage of T-cell epitope-based diagnostics and vaccines

BACKGROUND: T cells recognize a complex between a specific major histocompatibility complex (MHC) molecule and a particular pathogen-derived epitope. A given epitope will elicit a response only in individuals that express an MHC molecule capable of binding that particular epitope. MHC molecules are extremely polymorphic and over a thousand different human MHC (HLA) alleles are known. A disproportionate amount of MHC polymorphism occurs in positions constituting the peptide-binding region, and as a result, MHC molecules exhibit a widely varying binding specificity. In the design of peptide-based vaccines and diagnostics, the issue of population coverage in relation to MHC polymorphism is further complicated by the fact that different HLA types are expressed at dramatically different frequencies in different ethnicities. Thus, without careful consideration, a vaccine or diagnostic with ethnically biased population coverage could result. RESULTS: To address this issue, an algorithm was developed to calculate, on the basis of HLA genotypic frequencies, the fraction of individuals expected to respond to a given epitope set, diagnostic or vaccine. The population coverage estimates are based on MHC binding and/or T cell restriction data, although the tool can be utilized in a more general fashion. The algorithm was implemented as a web-application available at . CONCLUSION: We have developed a web-based tool to predict population coverage of T-cell epitope-based diagnostics and vaccines based on MHC binding and/or T cell restriction data. Accordingly, epitope-based vaccines or diagnostics can be designed to maximize population coverage, while minimizing complexity (that is, the number of different epitopes included in the diagnostic or vaccine), and also minimizing the variability of coverage obtained or projected in different ethnic groups

Magneto-transport properties of monolayer borophene in perpendicular magnetic field: influence of electron-phonon interaction

The magneto-transport properties of a borophene monolayer in a perpendicular magnetic field B are studied via calculating the conductivity tensor and resistance under electron-optical phonon interaction by using the linear response theory. Numerical results are obtained and discussed for some specific parameters. The magnetic field-dependent longitudinal conductivity shows the magneto-phonon resonance effect that describes the transition of electrons between Landau levels by absorbing/emitting an optical phonon. The Hall conductivity increases first and then decreases with the magnetic field strength. Also, the longitudinal resistance increases significantly with increasing temperature, which shows the metal behaviour of the material. Practically, the observed magneto-phonon resonance can be applied to experimentally determine some material parameters, such as the distance between Landau levels and the optical phonon energy

Protein sequence database for pathogenic arenaviruses

BACKGROUND: Arenaviruses are a family of rodent-borne viruses that cause several hemorrhagic fevers. These diseases can be devastating and are often lethal. Herein, to aid in the design and development of diagnostics, treatments and vaccines for arenavirus infections, we have developed a database containing protein sequences from the seven pathogenic arenaviruses (Junin, Guanarito, Sabia, Machupo, Whitewater Arroyo, Lassa and LCMV). RESULTS: The database currently contains a non-redundant set of 333 protein sequences which were manually annotated. All entries were linked to NCBI and cited PubMed references. The database has a convenient query interface including BLAST search. Sequence variability analyses were also performed and the results are hosted in the database. CONCLUSION: The database is available at and can be used to aid in studies that require proteomic information from pathogenic arenaviruses

A consensus epitope prediction approach identifies the breadth of murine T CD8+ -cell responses to vaccinia virus

The value of predictive algorithms for identifying CD8+ T (TCD8+)-cell epitopes has not been adequately tested experimentally. Here we demonstrate that conventional bioinformatic methods predict the vast majority of TCD8+-cell epitopes derived from vaccinia virus WR strain (VACV-WR) in the H-2b mouse model. This approach reveals the breadth of T-cell responses to vaccinia, a widely studied murine viral infection model, and may provide a tool for developing comprehensive antigenic maps of any complex pathogen

An ontology for immune epitopes: application to the design of a broad scope database of immune reactivities

BACKGROUND: Epitopes can be defined as the molecular structures bound by specific receptors, which are recognized during immune responses. The Immune Epitope Database and Analysis Resource (IEDB) project will catalog and organize information regarding antibody and T cell epitopes from infectious pathogens, experimental antigens and self-antigens, with a priority on NIAID Category A-C pathogens () and emerging/re-emerging infectious diseases. Both intrinsic structural and phylogenetic features, as well as information relating to the interactions of the epitopes with the host's immune system will be catalogued. DESCRIPTION: To effectively represent and communicate the information related to immune epitopes, a formal ontology was developed. The semantics of the epitope domain and related concepts were captured as a hierarchy of classes, which represent the general and specialized relationships between the various concepts. A complete listing of classes and their properties can be found at . CONCLUSION: The IEDB's ontology is the first ontology specifically designed to capture both intrinsic chemical and biochemical information relating to immune epitopes with information relating to the interaction of these structures with molecules derived from the host immune system. We anticipate that the development of this type of ontology and associated databases will facilitate rigorous description of data related to immune epitopes, and might ultimately lead to completely new methods for describing and modeling immune responses

Polyfunctional CD4+ T cell responses to a set of pathogenic arenaviruses provide broad population coverage

Background. Several arenaviruses cause severe hemorrhagic fever and aseptic meningitis in humans for which no licensed vaccines are available. A major obstacle for vaccine development is pathogen heterogeneity within the Arenaviridae family. Evidence in animal models and humans indicate that T cell and antibody-mediated immunity play important roles in controlling arenavirus infection and replication. Because CD4+T cells are needed for optimal CD8+T cell responses and to provide cognate help for B cells, knowledge of epitopes recognized by CD4+T cells is critical to the development of an effective vaccine strategy against arenaviruses. Thus, the goal of the present study was to define and characterize CD4+T cell responses from a broad repertoire of pathogenic arenaviruses (including lymphocytic choriomeningitis, Lassa, Guanarito, Junin, Machupo, Sabia, and Whitewater Arroyo viruses) and to provide determinants with the potential to be incorporated into a multivalent vaccine strategy. Results. By inoculating HLA-DRB1*0101 transgenic mice with a panel of recombinant vaccinia viruses, each expressing a single arenavirus antigen, we identified 37 human HLA-DRB1*0101-restricted CD4+T cell epitopes from the 7 antigenically distinct arenaviruses. We showed that the arenavirus-specific CD4+T cell epitopes are capable of eliciting T cells with a propensity to provide help and protection through CD40L and polyfunctional cytokine expression. Importantly, we demonstrated that the set of identified CD4+T cell epitopes provides broad, non-ethnically biased population coverage of all 7 arenavirus species targeted by our studies. Conclusions. The identification of CD4+T cell epitopes, with promiscuous binding properties, derived from 7 different arenavirus species will aid in the development of a T cell-based vaccine strategy with the potential to target a broad range of ethnicities within the general population and to protect against both Old and New World arenavirus infection. © 2010 Kotturi et al; licensee BioMed Central Ltd

A Community Resource Benchmarking Predictions of Peptide Binding to MHC-I Molecules

Recognition of peptides bound to major histocompatibility complex (MHC) class I molecules by T lymphocytes is an essential part of immune surveillance. Each MHC allele has a characteristic peptide binding preference, which can be captured in prediction algorithms, allowing for the rapid scan of entire pathogen proteomes for peptide likely to bind MHC. Here we make public a large set of 48,828 quantitative peptide-binding affinity measurements relating to 48 different mouse, human, macaque, and chimpanzee MHC class I alleles. We use this data to establish a set of benchmark predictions with one neural network method and two matrix-based prediction methods extensively utilized in our groups. In general, the neural network outperforms the matrix-based predictions mainly due to its ability to generalize even on a small amount of data. We also retrieved predictions from tools publicly available on the internet. While differences in the data used to generate these predictions hamper direct comparisons, we do conclude that tools based on combinatorial peptide libraries perform remarkably well. The transparent prediction evaluation on this dataset provides tool developers with a benchmark for comparison of newly developed prediction methods. In addition, to generate and evaluate our own prediction methods, we have established an easily extensible web-based prediction framework that allows automated side-by-side comparisons of prediction methods implemented by experts. This is an advance over the current practice of tool developers having to generate reference predictions themselves, which can lead to underestimating the performance of prediction methods they are not as familiar with as their own. The overall goal of this effort is to provide a transparent prediction evaluation allowing bioinformaticians to identify promising features of prediction methods and providing guidance to immunologists regarding the reliability of prediction tools

The Immune Epitope Database and Analysis Resource: From Vision to Blueprint

A planned repository of immune epitope data with associated analysis tools should be a boon to vaccine developmen