Computational Vaccinology

  • Matthew N. DaviesEmail author
  • Darren R. Flower
Part of the Immunomics Reviews: book series (IMMUN, volume 3)


In this chapter we shall review recent developments in computational vaccinology, highlighting work in the area of epitope and antigen identification, and the discovery of delivery vectors and adjuvants. These diverse activities all have the potential to reduce significantly the laboratory resource needed for efficient vaccine discovery. We discuss how computational analysis of pathogenic genomes by epitope mapping and reverse vaccinology can provide viable vaccine targets.


Major Histocompatibility Complex Visceral Leishmaniasis Cell Epitope Major Histocompatibility Complex Molecule CCR4 Antagonist 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Andersen PH et al (2006) Prediction of residues in discontinuous B Cell epitopes using protein 3D structures. Protein Sci 15:2558–2567CrossRefGoogle Scholar
  2. Babiuk LA et al (2000) Nucleic acid vaccines: research tool or commercial reality. Vet Immunol Immunopathol 76:1–23CrossRefPubMedGoogle Scholar
  3. Babiuk LA et al (2003) Induction of immune responses by DNA vaccines in large animals. Vaccine 21:649–658CrossRefPubMedGoogle Scholar
  4. Bateman A et al (2000) The Pfam protein families database. Nucleic Acids Res 28:263–266CrossRefPubMedGoogle Scholar
  5. Bissantz C (2003) Conformational changes of G protein-coupled receptors during their activation by agonist binding. J Recept Signal Transduct Res 23:123–153CrossRefPubMedGoogle Scholar
  6. Blythe MJ, Flower DR (2004) Benchmarking B Cell epitope prediction: underperformance of existing methods. Protein Sci 14:246–248CrossRefPubMedGoogle Scholar
  7. Booth JS et al (2007) Innate immune responses induced by classes of CpG oligodeoxynucleotides in ovine lymph node and blood mononuclear cells. Vet Immunol Immunopathol 115(1–2):24–34CrossRefPubMedGoogle Scholar
  8. Bulashevska A, Eils R (2006) Predicting protein subcellular locations using hierarchical ensemble of Bayesian classifiers based on Markov chains. BMC Bioinformatics. 7:298Google Scholar
  9. Charoenvit Y, Goel N, Whelan M, Rosenthal KS, Zimmerman DH (2004a) CEL-1000 – a peptide with adjuvant activity for Th1 immune responses. Vaccine 22(19):2368–2373CrossRefPubMedGoogle Scholar
  10. Charoenvit Y et al (2004b) A small peptide (CEL-1000) derived from the beta-chain of the human major histocompatibility complex class II molecule induces complete protection against malaria in an antigen-independent manner. Antimicrob Agents Chemother 48:2455–2463CrossRefPubMedGoogle Scholar
  11. Christopoulos A, Kenakin TG (2002) protein-coupled receptor allosterism and complexing. Pharmacol Rev 54:323–374CrossRefPubMedGoogle Scholar
  12. Chvatchko Y, Hoogewerf AJ, Meyer A, Alouani S, Juillard P, Buser R, Conquet F, Proudfoot AE, Wells TN, Power CA (2000) A key role for CC chemokine receptor 4 in lipopolysaccharide-induced endotoxic shock. J Exp Med 191:1755–1764CrossRefPubMedGoogle Scholar
  13. Davies MN et al (2003) A novel predictive technique for the MHC class II peptide-binding interaction. Mol Med 9:220–225CrossRefPubMedGoogle Scholar
  14. Davies MN et al (2006) Statistical deconvolution of enthalpic energetic contributions to MHC-peptide binding affinity. BMC Struct Biol 6:5–17CrossRefPubMedGoogle Scholar
  15. De Groot AS (2006) Immunomics: discovering new targets for vaccines and therapeutics. Drug Discov Today 11:203–209CrossRefPubMedGoogle Scholar
  16. de Lisle GW, Wards BJ, Buddle BM, Collins DM (2005) The efficacy of live tuberculosis vaccines after presensitization with Mycobacterium avium. Tuberculosis (Edinb) 85(1–2):73–79CrossRefGoogle Scholar
  17. Delcher AL et al (1999) Improved microbial gene identification with GLIMMER. Nucleic Acids Res 27:4636–4641CrossRefPubMedGoogle Scholar
  18. Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR (1996) Identification of a major co-receptor for primary isolates of HIV-1. Nature 381:661–666CrossRefPubMedGoogle Scholar
  19. Donnes P, Elofsson A (2002) Prediction of MHC class I binding peptides, using SVMHC. BMC Bioinformatics 3:25CrossRefPubMedGoogle Scholar
  20. Doytchinova IA, Flower DR (2007) VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinformatics 8:4CrossRefPubMedGoogle Scholar
  21. Doytchinova IA et al (2005) Towards the chemometric dissection of peptide-HLA-A*0201 binding affinity: comparison of local and global QSAR models. J Comput Aided Mol Des 19:203–212CrossRefPubMedGoogle Scholar
  22. Ebo DG, Bridts CH, Stevens WJ (2008) IgE-mediated large local reaction from recombinant hepatitis B vaccine. Allergy 63(4):483–484CrossRefPubMedGoogle Scholar
  23. Emanuelsson O, Brunak S, von Heijne G, Nielsen H (2007) Locating proteins in the cell using TargetP, SignalP and related tools. Nat Protoc 2(4):953–971CrossRefPubMedGoogle Scholar
  24. Falquet L et al (2002) The PROSITE database. Nucleic Acids Res 30:235–238CrossRefPubMedGoogle Scholar
  25. Feng Y, Broder CC, Kennedy PE, Berger EA (1996) HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272:872–877CrossRefPubMedGoogle Scholar
  26. Gether U, Asmar F, Meinild AK, Rasmussen SG (2002) Structural basis for activation of G-protein-coupled receptors. Pharmacol Toxicol 91:304–312CrossRefPubMedGoogle Scholar
  27. Girard MP, Osmanov SK, Kieny MP (2006) A review of vaccine research and development: the human immunodeficiency virus (HIV). Vaccine 24(19):4062–4081CrossRefPubMedGoogle Scholar
  28. Godessart N (2005) Chemokine receptors: attractive targets for drug discovery. Ann N Y Acad Sci 1051:647–657CrossRefPubMedGoogle Scholar
  29. Greenbaum JA, Andersen PH, Blythe M, Bui HH, Cachau RE, Crowe J, Davies MN et al (2007) Towards a consensus on datasets and evaluation metrics for developing B Cell epitope prediction tools. J Mol Recognit 20(2):75–82CrossRefPubMedGoogle Scholar
  30. Gupta RK (1998) Aluminum compounds as vaccine adjuvants. Adv Drug Deliv Rev 32:155–172CrossRefPubMedGoogle Scholar
  31. Guzmán E, Romeu A, Garcia-Vallve S (2008) Completely sequenced genomes of pathogenic bacteria: a review. Enferm Infecc Microbiol Clin 26(2):88–98CrossRefPubMedGoogle Scholar
  32. Harish N, Gupta R, Agarwal P, Scaria V, Pillai B (2006) DyNAVacS: an integrative tool for optimized DNA vaccine design. Nucleic Acids Res 34(Web Server issue):W264–W266CrossRefPubMedGoogle Scholar
  33. Hedrick JA, Zlotnik A (1996) Chemokines and lymphocyte biology. Curr Opin Immunol 8:343–347CrossRefPubMedGoogle Scholar
  34. Henry I, Sharp PM (2007) Predicting gene expression level from codon usage bias. Mol Biol Evol 24(1):10–12CrossRefPubMedGoogle Scholar
  35. Hung CF, Ma B, Monie A, Tsen SW, Wu TC (2008) Therapeutic human papillomavirus vaccines: current clinical trials and future directions. Expert Opin Biol Ther 8(4):421–439CrossRefPubMedGoogle Scholar
  36. Iellem A, Colantonio L, Bhakta S, Sozzani S, Mantovani A, Sinigaglia F, D’Ambrosio D (2001) Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4+CD25+ regulatory T cells. J Exp Med 194:847–854CrossRefPubMedGoogle Scholar
  37. Jardetzky TS et al (1996) Crystallographic analysis of endogenous peptides associated with HLADR1 suggests a common, polyproline II-like conformation for bound peptides. Proc Natl Acad Sci USA 93:734–738CrossRefPubMedGoogle Scholar
  38. Klinman DM et al (1997) Contribution of CpG motifs to the immunogenicity of DNA vaccines. J Immunol 158:3635–3639PubMedGoogle Scholar
  39. Kulkarni-Kale U, Bhosle S, Kolaskar AS (2005) CEP: a conformational epitope prediction server. Nucleic Acids Res 33(Web Server issue):W168–W171CrossRefPubMedGoogle Scholar
  40. Lee AH et al (1997) Comparison of various expression plasmids for the induction of immune response by DNA immunization. Mol Cells 7:495–501PubMedGoogle Scholar
  41. Lieberam I, Forster I (1999) The murine beta-chemokine TARC is expressed by subsets of dendritic cells and attracts primed CD4+ T cells. Eur J Immunol 29:2684–2694CrossRefPubMedGoogle Scholar
  42. Liu W et al (2006) Quantitative prediction of mouse class I MHC peptide binding affinity using support vector machine regression (SVR) models. BMC Bioinformatics 7:182CrossRefPubMedGoogle Scholar
  43. Locati M, Murphy PM (1999) Chemokines and chemokine receptors: biology and clinical relevance in inflammation and AIDS. Annu Rev Med 50:425–440CrossRefPubMedGoogle Scholar
  44. Luster AD (1998) Chemokines – chemotactic cytokines that mediate inflammation. N Engl J Med 338:436–445CrossRefPubMedGoogle Scholar
  45. Maione D et al (2005) Identification of a universal Group B streptococcus vaccine by multiple genome screen. Science 309:148–150CrossRefPubMedGoogle Scholar
  46. McMurry J et al (2005) Analyzing Mycobacterium tuberculosis proteomes for candidate vaccine epitopes. Tuberculosis (Edinb) 85:95–105CrossRefGoogle Scholar
  47. Merino EF, Fernandez-Becerra C, Durham AM, Ferreira JE, Tumilasci VF, d’Arc-Neves J, da Silva-Nunes M, Ferreira MU, Wickramarachchi T, Udagama-Randeniya P, Handunnetti SM, Del Portillo HA (2006) Multi-character population study of the vir subtelomeric multigene superfamily of Plasmodium vivax, a major human malaria parasite. Mol Biochem Parasitol 149(1):10–16CrossRefPubMedGoogle Scholar
  48. Mok BW, Ribacke U, Winter G, Yip BH, Tan CS, Fernandez V, Chen Q, Nilsson P, Wahlgren M (2007) Comparative transcriptomal analysis of isogenic Plasmodium falciparum clones of distinct antigenic and adhesive phenotypes. Mol Biochem Parasitol 151(2):184–192CrossRefPubMedGoogle Scholar
  49. Montigiani S et al (2002) Genomic approach for analysis of surface proteins in Chlamydia pneumoniae. Infect Immun 70:368–379CrossRefPubMedGoogle Scholar
  50. Noguchi H et al (2002) Hidden Markov model-based prediction of antigenic peptides that interact with MHC class II molecules. J Biosci Bioeng 94:264–270PubMedGoogle Scholar
  51. O’Hagan DT, MacKichan ML, Singh M (2001) Recent developments in adjuvants for vaccines against infectious diseases. Biomol Eng 18(3):69–85CrossRefPubMedGoogle Scholar
  52. Ou HY et al (2004) GS-Finder: a program to find bacterial gene start sites with a self-training method. Int J Biochem Cell Biol 36:535–544CrossRefPubMedGoogle Scholar
  53. Palma-Carlos AG, Santos AS, Branco-Ferreira M, Pregal AL, Palma-Carlos ML, Bruno ME, Falagiani P, Riva G (2006) Clinical efficacy and safety of preseasonal sublingual immunotherapy with grass pollen carbamylated allergoid in rhinitic patients. A double-blind, placebo-controlled study. Allergol Immunopathol (Madr) 34(5):194–198CrossRefGoogle Scholar
  54. Pizza M et al (2000a) Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 287:1816–1820CrossRefPubMedGoogle Scholar
  55. Pizza M et al (2000b) Whole genome sequencing to identify vaccine candidates against serogroup B meningococcus. Science 287:1816–1820CrossRefPubMedGoogle Scholar
  56. Ponomarenko JV, Bourne PE (2007) Antibody-protein interactions: benchmark datasets and prediction tools evaluation. BMC Struct Biol 7:64CrossRefPubMedGoogle Scholar
  57. Rammensee H et al (1999) SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 50:213–219CrossRefPubMedGoogle Scholar
  58. Rey S, Acab M, Gardy JL, Laird MR, deFays K, Lambert C, Brinkman FS (2005) PSORTdb: a protein subcellular localization database for bacteria. Nucleic Acids Res 33(Database issue):D164–D168CrossRefPubMedGoogle Scholar
  59. Rombel IT et al (2003) ORF-FINDER: a vector for high-throughput gene identification. Gene 282:33–41CrossRefGoogle Scholar
  60. Ross BC et al (2001) Identification of vaccine candidate antigens from a genomic analysis of Porphyromonas gingivalis. Vaccine 19:4135–4142CrossRefPubMedGoogle Scholar
  61. Salomon J, Flower DR (2006) Predicting Class II MHC-Peptide binding: a kernel based approach using similarity scores. BMC Bioinformatics 7:501CrossRefPubMedGoogle Scholar
  62. Schellhammer I, Rarey M (2004) FlexX-Scan: fast, structure-based virtual screening. Proteins 57(3):504–517CrossRefPubMedGoogle Scholar
  63. Schijns VE (2003) Mechanisms of vaccine adjuvant activity: initiation and regulation of immune responses by vaccine adjuvants. Vaccine 21:829–831CrossRefPubMedGoogle Scholar
  64. Schreiber A, Humbert M, Benz A, Dietrich U (2005) 3D-Epitope-Explorer (3DEX): localization of conformational epitopes within three-dimensional structures of proteins. J Comput Chem 26(9):879–887CrossRefPubMedGoogle Scholar
  65. Servant F et al (2002) ProDom: automated clustering of homologous domains. Brief Bioinform 3:246–251CrossRefPubMedGoogle Scholar
  66. Singh M, O’Hagan DT (2002) Recent advances in vaccine adjuvants. Pharm Res 19:715–728CrossRefPubMedGoogle Scholar
  67. Singh M, Srivastava I (2003) Advances in vaccine adjuvants for infectious diseases. Curr HIV Res 1:309–320CrossRefPubMedGoogle Scholar
  68. Stills HF Jr (2005) Adjuvants and antibody production: dispelling the myths associated with Freund’s complete and other adjuvants. ILAR J 46:280–293PubMedGoogle Scholar
  69. Tettelin H et al (2000) Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 287:1809–1815CrossRefPubMedGoogle Scholar
  70. Tongchusak S, Brusic V, Chaiyaroj SC (2008) Promiscuous T cell epitope prediction of Candida albicans secretory aspartyl proteinase family of proteins. Infect Genet Evol 8(4):467–473CrossRefPubMedGoogle Scholar
  71. Uchijima M et al (1998) Optimization of codon usage of plasmid DNA vaccine is required for the effective MHC class I-restricted T Cell responses against an intracellular bacterium. J Immunol 161:5594–5599PubMedGoogle Scholar
  72. Vekemans J, Ballou WR (2008) Plasmodium falciparum malaria vaccines in development. Expert Rev Vaccines 7(2):223–240CrossRefPubMedGoogle Scholar
  73. Vivona S, Bernante F, Filippini F.(2006) NERVE: new enhanced reverse vaccinology environment. BMC Biotechnol 6:35Google Scholar
  74. Wan S et al (2004) Large-scale molecular dynamics simulations of HLA-A*0201 complexed with a tumor-specific antigenic peptide: can the alpha3 and beta2m domains be neglected? J Comput Chem 25:1803–1813CrossRefPubMedGoogle Scholar
  75. Wan J et al (2006) SVRMHC prediction server for MHC-binding peptides. BMC Bioinformatics 7:463CrossRefPubMedGoogle Scholar
  76. Winnenburg R, Urban M, Beacham A, Baldwin TK, Holland S, Lindeberg M, Hansen H, Rawlings C, Hammond-Kosack KE, Köhler J (2008) PHI-base update: additions to the pathogen host interaction database. Nucleic Acids Res 36(Database issue):D572–D576PubMedGoogle Scholar
  77. Wizemann TM et al (2001) Use of a whole genome approach to identify vaccine molecules affording protection against Streptococcus pneumoniae infection. Infect Immun 69:1593–1598CrossRefPubMedGoogle Scholar
  78. Xu ZL et al (2001) Optimization of transcriptional regulatory elements for constructing plasmid vectors. Gene 272:149–156CrossRefPubMedGoogle Scholar
  79. Yang J, Chen L, Sun L, Yu J, Jin Q (2008) VFDB 2008 release: an enhanced web-based resource for comparative pathogenomics. Nucleic Acids Res 36(Database issue):D539–D542PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.The Jenner InstituteUniversity of OxfordComptonUK

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