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

Exploitation 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.

[1]  O. Lund,et al.  NetMHCpan, a method for MHC class I binding prediction beyond humans , 2008, Immunogenetics.

[2]  Anne S De Groot,et al.  Further progress on defining highly conserved immunogenic epitopes for a global HIV vaccine: HLA-A3-restricted GAIA vaccine epitopes , 2012, Human Vaccines & Immunotherapeutics.

[3]  Morten Nielsen,et al.  NetCTLpan: pan-specific MHC class I pathway epitope predictions , 2010, Immunogenetics.

[4]  P. Tongaonkar,et al.  A semi‐empirical method for prediction of antigenic determinants on protein antigens , 1990, FEBS letters.

[5]  Vladimir Brusic,et al.  Bioinformatics tools for identifying T-cell epitopes , 2004 .

[6]  R W Ellis,et al.  New technologies for making vaccines. , 1999, Vaccine.

[7]  Vasant Honavar,et al.  Predicting flexible length linear B-cell epitopes. , 2008, Computational systems bioinformatics. Computational Systems Bioinformatics Conference.

[8]  Joo Chuan Tong,et al.  Immunoinformatics: Current trends and future directions , 2009, Drug Discovery Today.

[9]  Gajendra P. S. Raghava,et al.  ProPred: prediction of HLA-DR binding sites , 2001, Bioinform..

[10]  Mahima,et al.  Leptospirosis-persistence of a dilemma: an overview with particular emphasis on trends and recent advances in vaccines and vaccination strategies. , 2012, Pakistan journal of biological sciences : PJBS.

[11]  Morten Nielsen,et al.  Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction , 2007, BMC Bioinformatics.

[12]  Sheila Davey,et al.  State of the world's vaccines and immunization , 2013 .

[13]  Jonathan M. Gershoni,et al.  Epitope Mapping , 2012, BioDrugs.

[14]  M. McElrath,et al.  Profiling immunity to HIV vaccines with systems biology. , 2012, Current opinion in HIV and AIDS.

[15]  Robert Tampé,et al.  The transporter associated with antigen processing TAP: structure and function , 1999, FEBS letters.

[16]  H. Ploegh,et al.  Getting the inside out: the transporter associated with antigen processing (TAP) and the presentation of viral antigen. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. V. Regenmortel,et al.  What is a B-cell epitope? , 2009 .

[18]  O. Lund,et al.  HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4+ T Cell Responses , 2010, PloS one.

[19]  P. Karplus,et al.  Prediction of chain flexibility in proteins , 1985, Naturwissenschaften.

[20]  J. Whitton,et al.  A multivalent minigene vaccine, containing B-cell, cytotoxic T-lymphocyte, and Th epitopes from several microbes, induces appropriate responses in vivo and confers protection against more than one pathogen , 1997, Journal of virology.

[21]  Andreas D. Baxevanis,et al.  Bioinformatics - a practical guide to the analysis of genes and proteins , 2001, Methods of biochemical analysis.

[22]  Rajat K De,et al.  Immunoinformatics: an integrated scenario , 2010, Immunology.

[23]  Gajendra P.S. Raghava,et al.  A hybrid approach for predicting promiscuous MHC class I restricted T cell epitopes , 2007, Journal of Biosciences.

[24]  Zhikai Xu,et al.  Immune responses induced in HHD mice by multiepitope HIV vaccine based on cryptic epitope modification , 2013, Molecular Biology Reports.

[25]  E. K. Jagusztyn-Krynicka,et al.  Proteomics for development of vaccine. , 2011, Journal of proteomics.

[26]  N. Russell,et al.  Novel directions in HIV-1 vaccines revealed from clinical trials. , 2013, Current opinion in HIV and AIDS.

[27]  P. Chan,et al.  Outbreak of avian influenza A(H5N1) virus infection in Hong Kong in 1997. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[28]  C DeLisi,et al.  T-cell antigenic sites tend to be amphipathic structures. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[29]  K. R. Woods,et al.  Prediction of protein antigenic determinants from amino acid sequences. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Immunoinformatics: Tools for Large-Scale Immunology , 2003 .

[31]  I. Ferlenghi,et al.  Structural vaccinology: a three-dimensional view for vaccine development. , 2013, Current topics in medicinal chemistry.

[32]  Karina Yusim,et al.  Immunoinformatics Comes of Age , 2006, PLoS Comput. Biol..

[33]  A. Jarzab,et al.  [Subunit vaccines--antigens, carriers, conjugation methods and the role of adjuvants]. , 2013, Postepy higieny i medycyny doswiadczalnej.

[34]  Immunogenic properties of a lettuce-derived C4(V3)6 multiepitopic HIV protein , 2013, Planta.

[35]  Yuxin Li,et al.  Pep-3D-Search: a method for B-cell epitope prediction based on mimotope analysis , 2008, BMC Bioinformatics.

[36]  A. D. De Groot,et al.  New tools, new approaches and new ideas for vaccine development , 2007, Expert Review of Vaccines.

[37]  Antônio M. Rezende,et al.  An assessment on epitope prediction methods for protozoa genomes , 2012, BMC Bioinformatics.

[38]  A. Shaw New technologies for new influenza vaccines. , 2012, Vaccine.

[39]  Y. Cheung,et al.  Two novel HLA-A*0201 T-cell epitopes in avian H5N1 viral nucleoprotein induced specific immune responses in HHD mice , 2009, Veterinary research.

[40]  S. Miller,et al.  A virus-induced molecular mimicry model of multiple sclerosis , 2001 .

[41]  E. Carter,et al.  Analyzing Mycobacterium tuberculosis proteomes for candidate vaccine epitopes. , 2005, Tuberculosis.

[42]  P. Palese,et al.  Toward a universal influenza virus vaccine: prospects and challenges. , 2013, Annual review of medicine.

[43]  Gajendra P.S. Raghava,et al.  Prediction of CTL epitopes using QM, SVM and ANN techniques. , 2004, Vaccine.

[44]  Avner Schlessinger,et al.  Towards a consensus on datasets and evaluation metrics for developing B‐cell epitope prediction tools , 2007, Journal of molecular recognition : JMR.

[45]  Vladimir Brusic,et al.  Evaluation of MHC-II peptide binding prediction servers: applications for vaccine research , 2008, BMC Bioinformatics.

[46]  Arne Elofsson,et al.  Prediction of MHC class I binding peptides, using SVMHC , 2002, BMC Bioinformatics.

[47]  C. Yun,et al.  Mechanisms of the Regulation of the Intestinal Na+/H+Exchanger NHE3 , 2009, Journal of biomedicine & biotechnology.

[48]  C. Foged,et al.  License to kill: Formulation requirements for optimal priming of CD8(+) CTL responses with particulate vaccine delivery systems. , 2012, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[49]  J. Sidney,et al.  Broad and Cross-Clade CD4+ T-Cell Responses Elicited by a DNA Vaccine Encoding Highly Conserved and Promiscuous HIV-1 M-Group Consensus Peptides , 2012, PloS one.

[50]  Bo Yao,et al.  Conformational B-Cell Epitope Prediction on Antigen Protein Structures: A Review of Current Algorithms and Comparison with Common Binding Site Prediction Methods , 2013, PloS one.

[51]  E. Reinherz,et al.  Prediction of peptide-MHC binding using profiles. , 2007, Methods in molecular biology.

[52]  H. Rammensee,et al.  Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules , 1991, Nature.

[53]  Morten Nielsen,et al.  Accurate approximation method for prediction of class I MHC affinities for peptides of length 8, 10 and 11 using prediction tools trained on 9mers , 2008, Bioinform..

[54]  C. Klade Proteomics approaches towards antigen discovery and vaccine development. , 2002, Current opinion in molecular therapeutics.

[55]  T. Liang,et al.  Development of a plant-derived subunit vaccine candidate against hepatitis C virus , 2000, Archives of Virology.

[56]  Lin Shen,et al.  Dose-response curve slope sets class-specific limits on inhibitory potential of anti-HIV drugs , 2008, Nature Medicine.

[57]  N. Michael,et al.  HIV-1 variable loop 2 and its importance in HIV-1 infection and vaccine development. , 2013, Current HIV research.

[58]  Chloroplast expression of an HIV envelop-derived multiepitope protein: towards a multivalent plant-based vaccine , 2013, Plant Cell, Tissue and Organ Culture (PCTOC).

[59]  Di Wu,et al.  SEPPA: a computational server for spatial epitope prediction of protein antigens , 2009, Nucleic Acids Res..

[60]  Vasant Honavar,et al.  A framework for developing epitope prediction tools , 2010, BCB '10.

[61]  L. K. Ely,et al.  Dissecting the role of peptides in the immune response: theory, practice and the application to vaccine design , 2003, Journal of peptide science : an official publication of the European Peptide Society.

[62]  David E. Anderson,et al.  Induction of Broad Cross-Subtype-Specific HIV-1 Immune Responses by a Novel Multivalent HIV-1 Peptide Vaccine in Cynomolgus Macaques , 2008, The Journal of Immunology.

[63]  John Moult,et al.  A decade of CASP: progress, bottlenecks and prognosis in protein structure prediction. , 2005, Current opinion in structural biology.

[64]  Morten Nielsen,et al.  Reliable B Cell Epitope Predictions: Impacts of Method Development and Improved Benchmarking , 2012, PLoS Comput. Biol..

[65]  Vasant G Honavar,et al.  Building classifier ensembles for B-cell epitope prediction. , 2014, Methods in molecular biology.

[66]  Manoj Bhasin,et al.  Analysis and prediction of affinity of TAP binding peptides using cascade SVM , 2004, Protein science : a publication of the Protein Society.

[67]  Anne S De Groot,et al.  Coupling sensitive in vitro and in silico techniques to assess cross-reactive CD4(+) T cells against the swine-origin H1N1 influenza virus. , 2011, Vaccine.

[68]  S. Z. Bathaie,et al.  Design and characterization of a chimeric multiepitope construct containing CfaB, heat‐stable toxoid, CssA, CssB, and heat‐labile toxin subunit B of enterotoxigenic Escherichia coli: a bioinformatic approach , 2014, Biotechnology and applied biochemistry.

[69]  E Westhof,et al.  Correlation between the location of antigenic sites and the prediction of turns in proteins. , 1993, Immunology letters.

[70]  Cecile Viboud,et al.  Impact of cross-protective vaccines on epidemiological and evolutionary dynamics of influenza , 2012, Proceedings of the National Academy of Sciences.

[71]  O. Lund,et al.  An integrative approach to CTL epitope prediction: A combined algorithm integrating MHC class I binding, TAP transport efficiency, and proteasomal cleavage predictions , 2005, European journal of immunology.

[72]  John Sidney,et al.  A Systematic Assessment of MHC Class II Peptide Binding Predictions and Evaluation of a Consensus Approach , 2008, PLoS Comput. Biol..

[73]  R. Zinkernagel,et al.  The discovery of MHC restriction. , 1997, Immunology today.

[74]  Sudipto Saha,et al.  Prediction of continuous B‐cell epitopes in an antigen using recurrent neural network , 2006, Proteins.

[75]  A. Takada,et al.  Cross-Protective Peptide Vaccine against Influenza A Viruses Developed in HLA-A*2402 Human Immunity Model , 2011, PloS one.

[76]  E. De Pauw,et al.  Advances in immunoproteomics for serological characterization of microbial antigens. , 2006, Journal of Microbiological Methods.

[77]  Pedro A Reche,et al.  Prediction of MHC-peptide binding: a systematic and comprehensive overview. , 2009, Current pharmaceutical design.

[78]  Streatfield Sj,et al.  Plant-based vaccines for animal health. , 2005 .

[79]  J M Ostell,et al.  The NCBI data model. , 2001, Methods of biochemical analysis.

[80]  Uthaman Gowthaman,et al.  In silico tools for predicting peptides binding to HLA-class II molecules: more confusion than conclusion. , 2008, Journal of proteome research.

[81]  Vasant Honavar,et al.  Recent advances in B-cell epitope prediction methods , 2010, Immunome research.

[82]  Robert T. Chen,et al.  Emerging Vaccine Informatics , 2011, Journal of biomedicine & biotechnology.

[83]  Bjoern Peters,et al.  Identifying MHC Class I Epitopes by Predicting the TAP Transport Efficiency of Epitope Precursors , 2003, The Journal of Immunology.

[84]  J. Seyer,et al.  Localization of protective epitopes within the pilin subunit of the Vibrio cholerae toxin-coregulated pilus , 1991, Infection and immunity.

[85]  D. Flower,et al.  Benchmarking B cell epitope prediction: Underperformance of existing methods , 2005, Protein science : a publication of the Protein Society.

[86]  Sunil Thomas,et al.  Vaccines based on structure-based design provide protection against infectious diseases , 2013, Expert review of vaccines.

[87]  Andrea Bergmann State Of The Worlds Vaccines And Immunization , 2016 .

[88]  Anne S De Groot,et al.  HIV vaccine development by computer assisted design: the GAIA vaccine. , 2005, Vaccine.

[89]  Vito Michele Fazio,et al.  Epitope-driven DNA vaccine design employing immunoinformatics against B-cell lymphoma: a biotech's challenge. , 2012, Biotechnology advances.

[90]  K. Chou,et al.  Prediction of linear B-cell epitopes using amino acid pair antigenicity scale , 2007, Amino Acids.

[91]  D. van Baarle,et al.  T Cell Responses to Viral Infections – Opportunities for Peptide Vaccination , 2014, Front. Immunol..

[92]  Peter Walden,et al.  Exact prediction of a natural T cell epitope , 1991, European journal of immunology.

[93]  Tin Wee Tan,et al.  Evolutionarily Conserved Protein Sequences of Influenza A Viruses, Avian and Human, as Vaccine Targets , 2007, PloS one.

[94]  Zhiqiang Ma,et al.  Bioinformatics Resources and Tools for Conformational B-Cell Epitope Prediction , 2013, Comput. Math. Methods Medicine.

[95]  Pingping Guan,et al.  EpiJen: a server for multistep T cell epitope prediction , 2006, BMC Bioinformatics.

[96]  Young Do Kwon,et al.  Residue-Level Prediction of HIV-1 Antibody Epitopes Based on Neutralization of Diverse Viral Strains , 2013, Journal of Virology.

[97]  Geneviève Boucher,et al.  HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation , 2009, Nature Medicine.

[98]  C. Sorzano,et al.  A Human Multi-Epitope Recombinant Vaccinia Virus as a Universal T Cell Vaccine Candidate against Influenza Virus , 2011, PloS one.

[99]  Y. Barenholz,et al.  A novel influenza subunit vaccine composed of liposome-encapsulated haemagglutinin/neuraminidase and IL-2 or GM-CSF. I. Vaccine characterization and efficacy studies in mice. , 1999, Vaccine.

[100]  Ann L Oberg,et al.  Systems biology approaches to new vaccine development. , 2011, Current opinion in immunology.

[101]  Arthur M. Lesk,et al.  Introduction to bioinformatics , 2002 .

[102]  Nora C. Toussaint,et al.  Universal peptide vaccines - optimal peptide vaccine design based on viral sequence conservation. , 2011, Vaccine.

[103]  Michael A. Gonzalez,et al.  From genome to vaccine: in silico predictions, ex vivo verification. , 2001, Vaccine.

[104]  Judy Lieberman,et al.  Mapping cross-clade HIV-1 vaccine epitopes using a bioinformatics approach. , 2003, Vaccine.

[105]  R. Hodges,et al.  New hydrophilicity scale derived from high-performance liquid chromatography peptide retention data: correlation of predicted surface residues with antigenicity and X-ray-derived accessible sites. , 1986, Biochemistry.

[106]  Rolf Apweiler,et al.  The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000 , 2000, Nucleic Acids Res..

[107]  E. Emini,et al.  Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide , 1985, Journal of virology.

[108]  Morten Nielsen,et al.  CTL epitopes for influenza A including the H5N1 bird flu; genome-, pathogen-, and HLA-wide screening. , 2007, Vaccine.

[109]  Pierre Baldi,et al.  PEPITO: improved discontinuous B-cell epitope prediction using multiple distance thresholds and half sphere exposure , 2008, Bioinform..

[110]  Á. Alpuche-Solís,et al.  Oral immunogenicity of tomato-derived sDPT polypeptide containing Corynebacterium diphtheriae, Bordetella pertussis and Clostridium tetani exotoxin epitopes , 2011, Plant Cell Reports.

[111]  J. C. Sundaramurthi,et al.  HLA-B*27:05-specific cytotoxic T lymphocyte epitopes in Indian HIV type 1C. , 2013, AIDS research and human retroviruses.

[112]  William Martin,et al.  Epitope-Based Immunome-Derived Vaccines: A Strategy for Improved Design and Safety , 2008, Clinical Applications of Immunomics.

[113]  Morten Nielsen,et al.  Improved method for predicting linear B-cell epitopes , 2006, Immunome research.

[114]  D. Vergani,et al.  Molecular mimicry and autoimmune liver disease: virtuous intentions, malign consequences. , 2001, Liver.

[115]  Bernd Mayer,et al.  Machine learning approaches for prediction of linear B‐cell epitopes on proteins , 2006, Journal of molecular recognition : JMR.