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Pangenomic Reverse Vaccinology

  • Claudio Donati
  • Duccio Medini
  • Rino Rappuoli
Chapter

Abstract

It has become possible to obtain the set of potentially expressed proteins from the DNA sequence and, using a combination of computational and experimental approaches, to select a list of the potential antigens to be tested in animal models. This chapter illustrates how such an innovative process, termed “Reverse Vaccinology” and first applied to the case of Neisseria meningitidis serogroup B, can dramatically increase the efficiency of vaccine development. Authors also demonstrate how new types of information obtained from genetic typing and antigen-based serological typing can support the vaccine development phase as well as the continued clinical surveillance needed upon the introduction of a new vaccine into the field.

Keywords

Single Nucleotide Polymorphism Ribosomal Binding Site Capsular Polysaccharide Localization Prediction Streptococcus Agalactiae 
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.

References

  1. Achtman M (2008) Evolution, population structure, and phylogeography of genetically monomorphic bacterial pathogens. Annu Rev Microbiol 62:53–70CrossRefPubMedGoogle Scholar
  2. Achtman M et al (2004) Microevolution and history of the plague bacillus, Yersinia pestis. Proc Natl Acad Sci USA 101(51):17837–17842CrossRefPubMedGoogle Scholar
  3. Alland D et al (2003) Modeling bacterial evolution with comparative-genome-based marker systems: application to Mycobacterium tuberculosis evolution and pathogenesis. J Bacteriol 185(11):3392–3399CrossRefPubMedGoogle Scholar
  4. Altschul SF et al (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25(17):3389–3402CrossRefPubMedGoogle Scholar
  5. Bard JB, Rhee SY (2004) Ontologies in biology: design, applications and future challenges. Nat Rev Genet 5(3):213–222CrossRefPubMedGoogle Scholar
  6. Barocchi MA et al (2006) A pneumococcal pilus influences virulence and host inflammatory responses. Proc Natl Acad Sci USA 103(8):2857–2862CrossRefPubMedGoogle Scholar
  7. Bendtsen JD et al (2004a) Feature-based prediction of non-classical and leaderless protein secretion. Protein Eng Des Sel 17(4):349–356CrossRefPubMedGoogle Scholar
  8. Bendtsen JD et al (2004b) Improved prediction of signal peptides: SignalP 3.0. J Mol Biol 340(4):783–795CrossRefPubMedGoogle Scholar
  9. Bendtsen JD et al (2005) Prediction of twin-arginine signal peptides. BMC Bioinform 6:167CrossRefGoogle Scholar
  10. Benson DA et al (2008) GenBank. Nucleic Acids Res 36(Database Issue):D25–D30Google Scholar
  11. Bentley SD et al (2007) Meningococcal genetic variation mechanisms viewed through comparative analysis of serogroup C strain FAM18. PLoS Genet 3(2):e23CrossRefPubMedGoogle Scholar
  12. Boeckmann B et al (2003) The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nucleic Acids Res 31(1):365–370CrossRefPubMedGoogle Scholar
  13. Brennan MJ, Shahin RD (1996) Pertussis antigens that abrogate bacterial adherence and elicit immunity. Am J Respir Crit Care Med 154(4 Pt 2):S145–S149PubMedGoogle Scholar
  14. Brochet M et al. (2006) Genomic diversity and evolution within the species Streptococcus agalactiae. Microbes Infect 8(5):1227–1243CrossRefPubMedGoogle Scholar
  15. Brzuszkiewicz E et al (2006) How to become a uropathogen: comparative genomic analysis of extraintestinal pathogenic Escherichia coli strains. Proc Natl Acad Sci USA 103(34):12879–12884CrossRefPubMedGoogle Scholar
  16. Cedano J et al (1997) Relation between amino acid composition and cellular location of proteins. J Mol Biol 266(3):594–600CrossRefPubMedGoogle Scholar
  17. Chen F et al (2007) Assessing performance of orthology detection strategies applied to eukaryotic genomes. PLoS ONE 2(4):e383CrossRefPubMedGoogle Scholar
  18. Christie PJ et al (2005) Biogenesis, architecture, and function of bacterial type IV secretion systems. Annu Rev Microbiol 59:451–485CrossRefPubMedGoogle Scholar
  19. Darling AC et al (2004) Mauve: multiple alignment of conserved genomic sequence with rearrangements. Genome Res 14(7):1394–1403CrossRefPubMedGoogle Scholar
  20. Delcher AL et al (1999) Improved microbial gene identification with GLIMMER. Nucleic Acids Res 27(23):4636–4641CrossRefPubMedGoogle Scholar
  21. Feil EJ et al (2001) Recombination within natural populations of pathogenic bacteria: short-term empirical estimates and long-term phylogenetic consequences. Proc Natl Acad Sci USA 98(1):182–187CrossRefPubMedGoogle Scholar
  22. Filliol I et al (2006) Global phylogeny of Mycobacterium tuberculosis based on single nucleotide polymorphism (SNP) analysis: insights into tuberculosis evolution, phylogenetic accuracy of other DNA fingerprinting systems, and recommendations for a minimal standard SNP set. J Bacteriol 188(2):759–772CrossRefPubMedGoogle Scholar
  23. Finn RD et al (2008) The Pfam protein families database. Nucleic Acids Res 36(Database issue):D281–D288PubMedGoogle Scholar
  24. Fitch WM (1970) Distinguishing homologous from analogous proteins. Syst Zool 19(2):99–113CrossRefPubMedGoogle Scholar
  25. Flicek P et al (2008) Ensembl 2008. Nucleic Acids Res 36(Database issue):D707–D714Google Scholar
  26. Frishman D et al (1998) Combining diverse evidence for gene recognition in completely sequenced bacterial genomes. Nucleic Acids Res 26(12):2941–2947CrossRefPubMedGoogle Scholar
  27. Gardy JL, Brinkman FS (2006) Methods for predicting bacterial protein subcellular localization. Nat Rev Microbiol 4(10):741–751CrossRefPubMedGoogle Scholar
  28. Gardy JL et al (2003) PSORT-B: Improving protein subcellular localization prediction for Gram-negative bacteria. Nucleic Acids Res 31(13):3613–3617CrossRefPubMedGoogle Scholar
  29. Gardy JL et al (2005) PSORTb v.2.0: expanded prediction of bacterial protein subcellular localization and insights gained from comparative proteome analysis. Bioinform 21(5):617–623CrossRefGoogle Scholar
  30. Giuliani MM et al (2006) A universal vaccine for serogroup B meningococcus. Proc Natl Acad Sci USA 103(29):10834–10839CrossRefPubMedGoogle Scholar
  31. Goldschneider I, Gotschlich EC, Artenstein MS (1969) Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med 129(6):1307–1326CrossRefPubMedGoogle Scholar
  32. Gutacker MM et al (2002) Genome-wide analysis of synonymous single nucleotide polymorphisms in Mycobacterium tuberculosis complex organisms: resolution of genetic relationships among closely related microbial strains. Genetics 162(4):1533–1543PubMedGoogle Scholar
  33. Haas BJ et al (2004) DAGchainer: a tool for mining segmental genome duplications and synteny. Bioinform 20(18):3643–3646CrossRefGoogle Scholar
  34. Haft DH, Selengut JD, White O (2003) The TIGRFAMs database of protein families. Nucleic Acids Res 31(1):371–373CrossRefPubMedGoogle Scholar
  35. Hogg JS et al (2007) Characterization and modeling of the Haemophilus influenzae core and supragenomes based on the complete genomic sequences of Rd and 12 clinical nontypeable strains. Genome Biol 8(6):R103CrossRefPubMedGoogle Scholar
  36. Holland IB, Schmitt L, Young J (2005) Type 1 protein secretion in bacteria, the ABC-transporter dependent pathway (review). Mol Membr Biol 22(1–2):29–39CrossRefPubMedGoogle Scholar
  37. Hood DW et al (1996) DNA repeats identify novel virulence genes in Haemophilus influenzae. Proc Natl Acad Sci USA 93(20):11121–11125CrossRefPubMedGoogle Scholar
  38. Hueck CJ (1998) Type III protein secretion systems in bacterial pathogens of animals and plants. Microbiol Mol Biol Rev 62(2):379–433PubMedGoogle Scholar
  39. Jodar L et al (2002) Development of vaccines against meningococcal disease. Lancet 359(9316):1499–1508CrossRefPubMedGoogle Scholar
  40. Juncker AS et al. (2003) Prediction of lipoprotein signal peptides in Gram-negative bacteria. Protein Sci 12(8):1652–1662CrossRefPubMedGoogle Scholar
  41. Kall L, Krogh A, Sonnhammer EL (2007) Advantages of combined transmembrane topology and signal peptide prediction-the Phobius web server. Nucleic Acids Res 35(Web Server issue):W429–W432CrossRefPubMedGoogle Scholar
  42. Koonin EV (2005) Orthologs, paralogs, and evolutionary genomics. Annu Rev Genet 39:309–338CrossRefPubMedGoogle Scholar
  43. Kurtz S et al (2004) Versatile and open software for comparing large genomes. Genome Biol 5(2):R12CrossRefPubMedGoogle Scholar
  44. LeMieux J et al (2006) RrgA and RrgB are components of a multisubunit pilus encoded by the Streptococcus pneumoniae rlrA pathogenicity islet. Infect Immun 74(4):2453–2456CrossRefPubMedGoogle Scholar
  45. Li L, Stoeckert CJ, Jr, Roos DS (2003) OrthoMCL: identification of ortholog groups for eukaryotic genomes. Genome Res 13(9):2178–2189CrossRefPubMedGoogle Scholar
  46. Lukashin AV, Borodovsky M (1998) GeneMark.hmm: new solutions for gene finding. Nucleic Acids Res 26(4):1107–1115CrossRefPubMedGoogle Scholar
  47. Lu P et al (2005) PA-GOSUB: a searchable database of model organism protein sequences with their predicted Gene Ontology molecular function and subcellular localization. Nucleic Acids Res 33(Database issue):D147–D153CrossRefPubMedGoogle Scholar
  48. Maiden MC et al (1998) Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci USA 95(6):3140–3145CrossRefPubMedGoogle Scholar
  49. Maione D et al (2005) Identification of a universal Group B streptococcus vaccine by multiple genome screen. Science 309(5731):148–150CrossRefPubMedGoogle Scholar
  50. Medini D, Covacci A, Donati C (2006) Protein homology network families reveal step-wise diversification of Type III and Type IV secretion systems. PLoS Comput Biol 2(12):e173CrossRefPubMedGoogle Scholar
  51. Medini D et al (2008) Microbiology in the post-genomic era. Nat Rev Microbiol 6(6):419–430PubMedGoogle Scholar
  52. Moorhead SM, Dykes GA, Cursons RT (2003) An SNP-based PCR assay to differentiate between Listeria monocytogenes lineages derived from phylogenetic analysis of the sigB gene. J Microbiol Methods 55(2):425–432CrossRefPubMedGoogle Scholar
  53. Moschioni M et al (2008) Streptococcus pneumoniae contains 3 rlrA pilus variants that are clonally related. J Infect Dis 197(6):888–896CrossRefPubMedGoogle Scholar
  54. Muzzi A et al (2008) Pilus operon evolution in Streptococcus pneumoniae is driven by positive selection and recombination. PLoS ONE 3(11):e3660.CrossRefPubMedGoogle Scholar
  55. Nelson AL et al (2007) RrgA is a pilus-associated adhesin in Streptococcus pneumoniae. Mol Microbiol 66(2):329–340CrossRefPubMedGoogle Scholar
  56. Nishi T, Ikemura T, Kanaya S (2005) GeneLook: a novel ab initio gene identification system suitable for automated annotation of prokaryotic sequences. Gene 346:115–125CrossRefPubMedGoogle Scholar
  57. Perna NT et al (2001) Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 409(6819):529–533CrossRefPubMedGoogle Scholar
  58. Pizza M et al (2000) Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 287(5459):1816–1820CrossRefPubMedGoogle Scholar
  59. Pugsley AP (1993) The complete general secretory pathway in gram-negative bacteria. Microbiol Rev 57(1):50–108PubMedGoogle Scholar
  60. Punta M, Ofran Y (2008) The rough guide to in silico function prediction, or how to use sequence and structure information to predict protein function. PLoS Comput Biol 4(10):e1000160CrossRefPubMedGoogle Scholar
  61. Rappuoli R (2000) Reverse vaccinology. Curr Opin Microbiol 3(5):445–450CrossRefPubMedGoogle Scholar
  62. Read TD et al (2002) Comparative genome sequencing for discovery of novel polymorphisms in Bacillus anthracis. Science 296(5575):2028–2033CrossRefPubMedGoogle Scholar
  63. Rey S et al (2005) PSORTdb: a protein subcellular localization database for bacteria. Nucleic Acids Res 33(Database issue):D164–D168CrossRefPubMedGoogle Scholar
  64. Robertson GA et al (2004) Identification and interrogation of highly informative single nucleotide polymorphism sets defined by bacterial multilocus sequence typing databases. J Med Microbiol 53(Pt 1):35–45CrossRefPubMedGoogle Scholar
  65. Rodriguez-Ortega MJ et al (2006) Characterization and identification of vaccine candidate proteins through analysis of the group A Streptococcus surface proteome. Nat Biotechnol 24(2):191–197CrossRefPubMedGoogle Scholar
  66. Ross SC et al (1987) Killing of Neisseria meningitidis by human neutrophils: implications for normal and complement-deficient individuals. J Infect Dis 155(6):1266–1275PubMedGoogle Scholar
  67. Roumagnac P et al (2006) Evolutionary history of Salmonella typhi. Science 314(5803): 1301–1304CrossRefPubMedGoogle Scholar
  68. Saunders NJ et al (1998) Simple sequence repeats in the Helicobacter pylori genome. Mol Microbiol 27(6):1091–1098CrossRefPubMedGoogle Scholar
  69. Selander RK et al (1986) Methods of multilocus enzyme electrophoresis for bacterial population genetics and systematics. Appl Environ Microbiol 51(5):873–884PubMedGoogle Scholar
  70. Serruto D, Rappuoli R (2006) Post-genomic vaccine development. FEBS Lett 580(12):2985–2992CrossRefPubMedGoogle Scholar
  71. Smith JM et al (1993) How clonal are bacteria? Proc Natl Acad Sci USA 90(10):4384–4388CrossRefGoogle Scholar
  72. Telford JL et al (2006) Pili in gram-positive pathogens. Nat Rev Microbiol 4(7):509–519CrossRefPubMedGoogle Scholar
  73. Tettelin H et al (2000) Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 287(5459):1809–1815CrossRefPubMedGoogle Scholar
  74. Tettelin H et al (2005) Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial “pan-genome”. Proc Natl Acad Sci USA 102(39):13950–13955CrossRefPubMedGoogle Scholar
  75. Tettelin H et al (2006) Towards a universal group B Streptococcus vaccine using multistrain genome analysis. Expert Rev Vaccines 5(5):687–694CrossRefPubMedGoogle Scholar
  76. Tettelin H et al (2008) Comparative genomics: the bacterial pan-genome. Curr Opin Microbiol 11(5):472–477CrossRefPubMedGoogle Scholar
  77. Thanassi DG et al (2005) Protein secretion in the absence of ATP: the autotransporter, two-partner secretion and chaperone/usher pathways of gram-negative bacteria (review). Mol Membr Biol 22(1–2):63–72CrossRefPubMedGoogle Scholar
  78. The UniProt Consortium (2008) The universal protein resource (UniProt). Nucleic Acids Res 36(Database issue):D190–D195Google Scholar
  79. Thompson JR et al (2005) Genotypic diversity within a natural coastal bacterioplankton population. Science 307(5713):1311–1313CrossRefPubMedGoogle Scholar
  80. Weissman SJ et al (2003) Enterobacterial adhesins and the case for studying SNPs in bacteria. Trends Microbiol 11(3):115–117CrossRefPubMedGoogle Scholar
  81. Welch RA et al (2002) Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc Natl Acad Sci USA 99(26):17020–17024CrossRefPubMedGoogle Scholar
  82. Yu CS, Lin CJ, Hwang JK (2004) Predicting subcellular localization of proteins for Gram-negative bacteria by support vector machines based on n-peptide compositions. Protein Sci 13(5):1402–1406CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Claudio Donati
    • 1
  • Duccio Medini
    • 1
  • Rino Rappuoli
    • 1
  1. 1.Novartis Vaccines and DiagnosticsSienaItaly

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