Innovative bioinformatic approaches for developing peptide‐based vaccines against hypervariable viruses

The application of the fields of pharmacogenomics and pharmacogenetics to vaccine design has been recently labeled ‘vaccinomics’. This newly named area of vaccine research, heavily intertwined with bioinformatics, seems to be leading the charge in developing novel vaccines for currently unmet medical needs against hypervariable viruses such as human immunodeficiency virus (HIV), hepatitis C and emerging avian and swine influenza. Some of the more recent bioinformatic approaches in the area of vaccine research include the use of epitope determination and prediction algorithms for exploring the use of peptide epitopes as vaccine immunogens. This paper briefly discusses and explores some current uses of bioinformatics in vaccine design toward the pursuit of peptide vaccines for hypervariable viruses. The various informatics and vaccine design strategies attempted by other groups toward hypervariable viruses will also be briefly examined, along with the strategy used by our group in the design and synthesis of peptide immunogens for candidate HIV and influenza vaccines.

[1]  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.

[2]  Gary J. Nabel,et al.  Preserved CD4+ Central Memory T Cells and Survival in Vaccinated SIV-Challenged Monkeys , 2006, Science.

[3]  O. Branch,et al.  Identification of T and B cell epitopes recognized by humans in the C-terminal 42-kDa domain of the Plasmodium falciparum merozoite surface protein (MSP)-1. , 1995, Journal of immunology.

[4]  Tobias Lang,et al.  Model-Based Design of Growth-Attenuated Viruses , 2006, PLoS Comput. Biol..

[5]  David J Brayden,et al.  Keynote review: intestinal Peyer's patch M cells and oral vaccine targeting. , 2005, Drug discovery today.

[6]  J. Kahn,et al.  Antibody and cellular immune responses in breakthrough infection subjects after HIV type 1 glycoprotein 120 vaccination. , 1999, AIDS research and human retroviruses.

[7]  Channa K. Hattotuwagama,et al.  Statistical deconvolution of enthalpic energetic contributions to MHC-peptide binding affinity , 2006, BMC Structural Biology.

[8]  O. Lund,et al.  Prediction of residues in discontinuous B‐cell epitopes using protein 3D structures , 2006, Protein science : a publication of the Protein Society.

[9]  T. Gibson,et al.  Systematic Discovery of New Recognition Peptides Mediating Protein Interaction Networks , 2005, PLoS biology.

[10]  J. R. Green,et al.  Global investigation of protein–protein interactions in yeast Saccharomyces cerevisiae using re-occurring short polypeptide sequences , 2008, Nucleic acids research.

[11]  G. Pape,et al.  T cell recognition of hepatitis B and C viral antigens , 1994, European journal of clinical investigation.

[12]  Hidemi Takahashi.  Antigen presentation in vaccine development. , 2003, Comparative immunology, microbiology and infectious diseases.

[13]  Ali Azizi,et al.  Characterization of liver histopathology in a transgenic mouse model expressing genotype 1a hepatitis C virus core and envelope proteins 1 and 2. , 2005, The Journal of general virology.

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

[15]  B. Walker,et al.  Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of persons with stable nonprogressing HIV type 1 infection. , 1996, AIDS research and human retroviruses.

[16]  Todd M. Allen,et al.  Increased Sequence Diversity Coverage Improves Detection of HIV-Specific T Cell Responses1 , 2007, The Journal of Immunology.

[17]  G. Nabel.  HIV vaccine strategies. , 2002, Vaccine.

[18]  Erwin L Roggen,et al.  An in silico method using an epitope motif database for predicting the location of antigenic determinants on proteins in a structural context , 2006, Journal of molecular recognition : JMR.

[19]  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.

[20]  James McCluskey,et al.  More than one reason to rethink the use of peptides in vaccine design , 2007, Nature Reviews Drug Discovery.

[21]  H. Katinger,et al.  Antibodies to conserved epitopes of the HIV-1 envelope in sera from long-term non-progressors: prevalence and association with neutralizing activity , 2006, AIDS.

[22]  Anne S De Groot,et al.  Engineering immunogenic consensus T helper epitopes for a cross-clade HIV vaccine. , 2004, Methods.

[23]  Yoram Louzoun,et al.  Virus-epitope vaccine design: informatic matching the HLA-I polymorphism to the virus genome. , 2007, Molecular immunology.

[24]  Ellis L. Reinherz,et al.  PEPVAC: a web server for multi-epitope vaccine development based on the prediction of supertypic MHC ligands , 2005, Nucleic Acids Res..

[25]  S. Zolla-Pazner,et al.  Conserved and Exposed Epitopes on Intact, Native, Primary Human Immunodeficiency Virus Type 1 Virions of Group M , 2000, Journal of Virology.

[26]  T. Matano,et al.  Involvement of Multiple Epitope-Specific Cytotoxic T-Lymphocyte Responses in Vaccine-Based Control of Simian Immunodeficiency Virus Replication in Rhesus Macaques , 2006, Journal of Virology.

[27]  B. Haynes,et al.  Synthetic peptide in mineral oil adjuvant elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes in rhesus monkeys. , 1993, Journal of immunology.

[28]  R. Siliciano,et al.  An algorithm for evaluating human cytotoxic T lymphocyte responses to candidate AIDS vaccines. , 1999, AIDS research and human retroviruses.

[29]  Ji Wan,et al.  SVRMHC prediction server for MHC-binding peptides , 2006, BMC Bioinformatics.

[30]  Albert Chan,et al.  PIPE: a protein-protein interaction prediction engine based on the re-occurring short polypeptide sequences between known interacting protein pairs , 2006, BMC Bioinformatics.

[31]  N. Q. Lu.  A speculative view of immune recognition. , 1994, Immunological investigations.

[32]  T. Hanai,et al.  Hidden Markov model-based prediction of antigenic peptides that interact with MHC class II molecules. , 2002, Journal of bioscience and bioengineering.

[33]  David A Winkler,et al.  Predictive Bayesian neural network models of MHC class II peptide binding. , 2005, Journal of molecular graphics & modelling.

[34]  K. Subbarao,et al.  Live attenuated vaccines for pandemic influenza. , 2009, Current topics in microbiology and immunology.

[35]  D. E. Anderson,et al.  Hypervariable epitope constructs representing variability in envelope glycoprotein of SIV induce a broad humoral immune response in rabbits and rhesus macaques. , 1998, AIDS research and human retroviruses.

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

[37]  S. Rowland-Jones,et al.  Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi. , 1998, The Journal of clinical investigation.

[38]  W. Fiers,et al.  A "universal" human influenza A vaccine. , 2004, Virus research.

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

[40]  A. Sette,et al.  Development of experimental carbohydrate-conjugate vaccines composed of Streptococcus pneumoniae capsular polysaccharides and the universal helper T-lymphocyte epitope (PADRE). , 2004, Vaccine.

[41]  A. Mccarthy.  Development , 1996, Current Opinion in Neurobiology.

[42]  L. Corey,et al.  HIV vaccines: new frontiers in vaccine development. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[43]  B. Snel,et al.  Conservation of gene order: a fingerprint of proteins that physically interact. , 1998, Trends in biochemical sciences.

[44]  Wen Liu,et al.  Quantitative prediction of mouse class I MHC peptide binding affinity using support vector machine regression (SVR) models , 2006, BMC Bioinformatics.

[45]  Darren R. Flower,et al.  Bioinformatics for Vaccinology , 2008 .

[46]  A. Golshani,et al.  Detection of influenza A and B neutralizing antibodies in vaccinated ferrets and macaques using specific biotin-streptavidin conjugated antibodies. , 2010, Journal of virological methods.

[47]  J. Lambert,et al.  A Phase I safety and immunogenicity trial of UBI microparticulate monovalent HIV-1 MN oral peptide immunogen with parenteral boost in HIV-1 seronegative human subjects. , 2001, Vaccine.

[48]  B. Haynes,et al.  Safety and immunogenicity of a CTL multiepitope peptide vaccine for HIV with or without GM-CSF in a phase I trial. , 2009, Vaccine.

[49]  A S Kolaskar,et al.  Prediction of three-dimensional structure and mapping of conformational epitopes of envelope glycoprotein of Japanese encephalitis virus. , 1999, Virology.

[50]  Matthew N Davies,et al.  Harnessing bioinformatics to discover new vaccines. , 2007, Drug discovery today.

[51]  Urmila Kulkarni-Kale,et al.  CEP: a conformational epitope prediction server , 2005, Nucleic Acids Res..

[52]  H. Kiyono,et al.  Comprehensive Gene Expression Profiling of Peyer’s Patch M Cells, Villous M-Like Cells, and Intestinal Epithelial Cells1 , 2008, The Journal of Immunology.

[53]  D. Eisenberg,et al.  Assigning protein functions by comparative genome analysis: protein phylogenetic profiles. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[54]  W. Fiers,et al.  M2e-based universal influenza A vaccine. , 2009, Vaccine.

[55]  R. Paranjape,et al.  Enhanced mucosal and systemic immune response with intranasal immunization of mice with HIV peptides entrapped in PLG microparticles in combination with Ulex Europaeus-I lectin as M cell target. , 2005, Vaccine.

[56]  Shixia Wang,et al.  Preclinical evaluation of cellular immune responses elicited by a polyvalent DNA prime/protein boost HIV-1 vaccine. , 2006, Virology.

[57]  Rino Rappuoli,et al.  Reverse Vaccinology and Genomics , 2003, Science.

[58]  M. Neutra,et al.  Human Intestinal M Cells Display the Sialyl Lewis A Antigen , 1999, Infection and Immunity.

[59]  Hui Lu,et al.  MULTIPROSPECTOR: An algorithm for the prediction of protein–protein interactions by multimeric threading , 2002, Proteins.

[60]  Adam J. Smith,et al.  The Database of Interacting Proteins: 2004 update , 2004, Nucleic Acids Res..

[61]  U. Kulkarni-Kale.  Prediction of 3D structure and function of proteins and peptides , 2003 .

[62]  Dong-Soo Han,et al.  PreSPI: a domain combination based prediction system for protein-protein interaction. , 2004, Nucleic acids research.

[63]  Irini A. Doytchinova,et al.  Towards the chemometric dissection of peptide – HLA-A*0201 binding affinity: comparison of local and global QSAR models , 2005, J. Comput. Aided Mol. Des..

[64]  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.

[65]  Lars Fugger,et al.  In Vivo Enhancement of Peptide Display by MHC Class II Molecules with Small Molecule Catalysts of Peptide Exchange1 , 2009, The Journal of Immunology.

[66]  H. Rammensee,et al.  SYFPEITHI: database for MHC ligands and peptide motifs , 1999, Immunogenetics.

[67]  T. Ben-Yedidia,et al.  Old and new vaccine approaches. , 2003, International immunopharmacology.

[68]  D. Montefiori,et al.  Effect of Plasmid DNA Vaccine Design and In Vivo Electroporation on the Resulting Vaccine-Specific Immune Responses in Rhesus Macaques , 2007, Journal of Virology.

[69]  A. Telesnitsky,et al.  The Remarkable Frequency of Human Immunodeficiency Virus Type 1 Genetic Recombination , 2009, Microbiology and Molecular Biology Reviews.

[70]  T. Ide,et al.  Phase I clinical study of a peptide vaccination for hepatitis C virus‐infected patients with different human leukocyte antigen‐class I‐A alleles , 2009, Cancer science.

[71]  B. Walker,et al.  Cytotoxic T lymphocytes in asymptomatic long-term nonprogressing HIV-1 infection. Breadth and specificity of the response and relation to in vivo viral quasispecies in a person with prolonged infection and low viral load. , 1996, Journal of immunology.

[72]  P. Fultz,et al.  Immune response of chimpanzees after immunization with the inactivated whole immunodeficiency virus (HIV-1), three different adjuvants and challenge. , 1993, Vaccine.

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

[74]  H. Grey,et al.  Prediction of major histocompatibility complex binding regions of protein antigens by sequence pattern analysis. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[75]  Z. Weng,et al.  Ancestral and consensus envelope immunogens for HIV-1 subtype C. , 2006, Virology.

[76]  Bjoern Peters,et al.  Ab and T cell epitopes of influenza A virus, knowledge and opportunities , 2007, Proceedings of the National Academy of Sciences.

[77]  F. Diaz-Mitoma,et al.  Viral peptide immunogens: current challenges and opportunities , 2007, Journal of peptide science : an official publication of the European Peptide Society.

[78]  H Robert Bergen,et al.  Discovery of naturally processed and HLA-presented class I peptides from vaccinia virus infection using mass spectrometry for vaccine development. , 2009, Vaccine.

[79]  F. Diaz-Mitoma,et al.  Potency of Cell-Mediated Immune Responses to Different Combined HIV-1 Immunogens in a Humanized Murine Model , 2005, Human vaccines.

[80]  H. Schuitemaker,et al.  Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics , 1995, The Journal of experimental medicine.

[81]  Feng Gao,et al.  Diversity Considerations in HIV-1 Vaccine Selection , 2002, Science.

[82]  G. d’Ettorre,et al.  Neutralizing Antibodies against Autologous Human Immunodeficiency Virus Type 1 Isolates in Patients with Increasing CD4 Cell Counts despite Incomplete Virus Suppression during Antiretroviral Treatment , 2001, Clinical Diagnostic Laboratory Immunology.

[83]  J. Mosqueda,et al.  In silico predicted conserved B-cell epitopes in the merozoite surface antigen-2 family of B. bovis are neutralization sensitive. , 2010, Veterinary parasitology.

[84]  Juwen Shen,et al.  Predicting protein–protein interactions based only on sequences information , 2007, Proceedings of the National Academy of Sciences.

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

[86]  R. Jacobson,et al.  Application of pharmacogenomics to vaccines. , 2009, Pharmacogenomics.

[87]  Jan Holmgren,et al.  Mucosal immunity and vaccines , 2005, Nature Medicine.

[88]  Xiping Wei,et al.  Human Immunodeficiency Virus Type 1 env Clones from Acute and Early Subtype B Infections for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies , 2005, Journal of Virology.

[89]  John Sidney,et al.  A Rational Strategy to Design Multiepitope Immunogens Based on Multiple Th Lymphocyte Epitopes1 , 2002, The Journal of Immunology.

[90]  David L. Robertson,et al.  An Isolate of Human Immunodeficiency Virus Type 1 Originally Classified as Subtype I Represents a Complex Mosaic Comprising Three Different Group M Subtypes (A, G, and I) , 1998, Journal of Virology.

[91]  A Sette,et al.  The development of multi-epitope vaccines: epitope identification, vaccine design and clinical evaluation. , 2001, Biologicals : journal of the International Association of Biological Standardization.

[92]  A. Sette,et al.  Recognition of Variant HIV-1 Epitopes from Diverse Viral Subtypes by Vaccine-Induced CTL1 , 2004, The Journal of Immunology.

[93]  A Tramontano,et al.  Mapping epitopes on protein surfaces. , 1995, Biopolymers.

[94]  Anne S. De Groot,et al.  Immunomics: discovering new targets for vaccines and therapeutics , 2006 .

[95]  ANDREAS SCHREIBER,et al.  3D‐Epitope‐Explorer (3DEX): Localization of conformational epitopes within three‐dimensional structures of proteins , 2005, J. Comput. Chem..

[96]  R. Rappuoli,et al.  Reverse vaccinology, a genome-based approach to vaccine development. , 2001 .

[97]  Shunsuke Kimura,et al.  Uptake through glycoprotein 2 of FimH+ bacteria by M cells initiates mucosal immune response , 2009, Nature.

[98]  V. Vasilevko,et al.  Prototype Alzheimer’s Disease Vaccine Using the Immunodominant B Cell Epitope from β-Amyloid and Promiscuous T Cell Epitope Pan HLA DR-Binding Peptide1 , 2005, The Journal of Immunology.

[99]  Ioannis Xenarios,et al.  DIP: The Database of Interacting Proteins: 2001 update , 2001, Nucleic Acids Res..

[100]  Anne S De Groot,et al.  Immunomics: discovering new targets for vaccines and therapeutics. , 2006, Drug discovery today.

[101]  J. Ulmer,et al.  Neutralizing antibody responses to HIV: role in protective immunity and challenges for vaccine design , 2004, Expert review of vaccines.

[102]  B. Murphy,et al.  Principles underlying the development and use of live attenuated cold-adapted influenza A and B virus vaccines. , 2002, Viral immunology.

[103]  H. Kiyono,et al.  Mucosal vaccines: novel advances in technology and delivery , 2009, Expert review of vaccines.

[104]  David E. Anderson,et al.  Immunogenicity of a polyvalent HIV-1 candidate vaccine based on fourteen wild type gp120 proteins in golden hamsters , 2006, BMC Immunology.

[105]  N. Nagelkerke,et al.  An Integrative Bioinformatic Approach for Studying Escape Mutations in Human Immunodeficiency Virus Type 1 gag in the Pumwani Sex Worker Cohort , 2007, Journal of Virology.

[106]  Anne S De Groot,et al.  From genome to vaccine--new immunoinformatics tools for vaccine design. , 2004, Methods.