Jenner-predict server: prediction of protein vaccine candidates (PVCs) in bacteria based on host-pathogen interactions

BMC Bioinformatics

Varun Jaiswal¹  Sree Krishna Chanumolu¹  Ankit Gupta¹  Rajinder S Chauhan¹  Chittaranjan Rout¹ 

[1] Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh 173234, India

关键词: Virulence;    Reverse vaccinology;    Antigen;    Domain;    Host-pathogen interactions;    Protein vaccine candidates (PVCs);   

Others  :  1087825
DOI  :  10.1186/1471-2105-14-211

 received in 2012-06-25, accepted in 2013-06-20,  发布年份 2013

【 摘 要 】

Background

Subunit vaccines based on recombinant proteins have been effective in preventing infectious diseases and are expected to meet the demands of future vaccine development. Computational approach, especially reverse vaccinology (RV) method has enormous potential for identification of protein vaccine candidates (PVCs) from a proteome. The existing protective antigen prediction software and web servers have low prediction accuracy leading to limited applications for vaccine development. Besides machine learning techniques, those software and web servers have considered only protein’s adhesin-likeliness as criterion for identification of PVCs. Several non-adhesin functional classes of proteins involved in host-pathogen interactions and pathogenesis are known to provide protection against bacterial infections. Therefore, knowledge of bacterial pathogenesis has potential to identify PVCs.

Results

A web server, Jenner-Predict, has been developed for prediction of PVCs from proteomes of bacterial pathogens. The web server targets host-pathogen interactions and pathogenesis by considering known functional domains from protein classes such as adhesin, virulence, invasin, porin, flagellin, colonization, toxin, choline-binding, penicillin-binding, transferring-binding, fibronectin-binding and solute-binding. It predicts non-cytosolic proteins containing above domains as PVCs. It also provides vaccine potential of PVCs in terms of their possible immunogenicity by comparing with experimentally known IEDB epitopes, absence of autoimmunity and conservation in different strains. Predicted PVCs are prioritized so that only few prospective PVCs could be validated experimentally. The performance of web server was evaluated against known protective antigens from diverse classes of bacteria reported in Protegen database and datasets used for VaxiJen server development. The web server efficiently predicted known vaccine candidates reported from Streptococcus pneumoniae and Escherichia coli proteomes. The Jenner-Predict server outperformed NERVE, Vaxign and VaxiJen methods. It has sensitivity of 0.774 and 0.711 for Protegen and VaxiJen dataset, respectively while specificity of 0.940 has been obtained for the latter dataset.

Conclusions

Better prediction accuracy of Jenner-Predict web server signifies that domains involved in host-pathogen interactions and pathogenesis are better criteria for prediction of PVCs. The web server has successfully predicted maximum known PVCs belonging to different functional classes. Jenner-Predict server is freely accessible at http://117.211.115.67/vaccine/home.html webcite

【 授权许可】

   
2013 Jaiswal et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Tarca AL, Carey VJ, Chen XW, Romero R, Drăghici S: Machine learning and its applications to biology. PLoS Comput Biol 2007, 3:e116.
• [2]Kimman TG: Risks connected with the use of conventional and genetically engineered vaccines. Vet Q 1992, 14:110-118.
• [3]Rappuoli R: Reverse vaccinology. Curr Opin Microbiol 2000, 3:445-450.
• [4]Gay CG, Zuerner R, Bannantine JP, Lillehoj HS, Zhu JJ, Green R, Pastoret PP: Genomics and vaccine development. Rev Sci Tech 2007, 26:49-67.
• [5]Pizza M, Scarlato V, Masignani V, Giuliani MM, Aricò B, Comanducci M, Jennings GT, Baldi L, Bartolini E, Capecchi B, Galeotti CL, Luzzi E, Manetti R, Marchetti E, Mora M, Nuti S, Ratti G, Santini L, Savino S, Scarselli M, Storni E, Zuo P, Broeker M, Hundt E, Knapp B, Blair E, Mason T, Tettelin H, Hood DW, Jeffries AC, Saunders NJ, Granoff DM, Venter JC, Moxon ER, Grandi G, Rappuoli R: Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 2000, 287:1816-1820.
• [6]Chakravarti DN, Fiske MJ, Fletcher LD, Zagursky RJ: Application of genomics and proteomics for identification of bacterial gene products as potential vaccine candidates. Vaccine 2000, 19:601-6012.
• [7]Wizemann TM, Heinrichs JH, Adamou JE, Erwin AL, Kunsch C, Choi GH, Barash SC, Rosen CA, Masure HR, Tuomanen E, Gayle A, Brewah YA, Walsh W, Barren P, Lathigra R, Hanson M, Langermann S, Johnson S, Koenig S: Use of a whole genome approach to identify vaccine molecules affording protection against Streptococcus pneumoniae infection. Infect Immun 2001, 69:1593-1598.
• [8]Ross BC, Czajkowski L, Hocking D, Margetts M, Webb E, Rothel L, Patterson M, Agius C, Camuglia S, Reynolds E, Littlejohn T, Gaeta B, Ng A, Kuczek ES, Mattick JS, Gearing D, Barr IG: Identification of vaccine candidate antigens from a genomic analysis of Porphyromonas gingivalis. Vaccine 2001, 19:4135-4142.
• [9]Montigiani S, Falugi F, Scarselli M, Finco O, Petracca R, Galli G, Mariani M, Manetti R, Agnusdei M, Cevenini R, Donati M, Nogarotto R, Norais N, Garaguso I, Nuti S, Saletti G, Rosa D, Ratti G, Grandi G: Genomic approach for analysis of surface proteins in Chlamydia pneumoniae. Infect Immun 2002, 70:368-379.
• [10]Ariel N, Zvi A, Grosfeld H, Gat O, Inbar Y, Velan B, Cohen S, Shafferman A: Search for potential vaccine candidate open reading frames in the Bacillus anthracis virulence plasmid pXO1: in silico and in vitro screening. Infect Immun 2002, 70:6817-6827.
• [11]Giuliani MM, Adu-Bobie J, Comanducci M, Aricò B, Savino S, Santini L, Brunelli B, Bambini S, Biolchi A, Capecchi B, Cartocci E, Ciucchi L, Di Marcello F, Ferlicca F, Galli B, Luzzi E, Masignani V, Serruto D, Veggi D, Contorni M, Morandi M, Bartalesi A, Cinotti V, Mannucci D, Titta F, Ovidi E, Welsch JA, Granoff D, Rappuoli R, Pizza M: A universal vaccine for serogroup B meningococcus. Proc Natl Acad Sci USA 2006, 103:10834-10839.
• [12]Gowthaman U, Agrewala JN: In silico tools for predicting peptides binding to HLA-class II molecules: more confusion than conclusion. J Proteome Res 2008, 7:154-163.
• [13]Zhang H, Wang P, Papangelopoulos N, Xu Y, Sette A, Bourne PE, Lund O, Ponomarenko J, Nielsen M, Peters B: Limitations of Ab initio predictions of peptide binding to MHC class II molecules. PLoS One 2010, 5:e9272.
• [14]Ponomarenko JV, Bourne PE: Antibody-protein interactions: benchmark datasets and prediction tools evaluation. BMC Struct Biol 2007, 7:64. BioMed Central Full Text
• [15]Blythe MJ, Flower DR: Benchmarking B cell epitope prediction: underperformance of existing methods. Protein Sci 2005, 14:246-248.
• [16]Doytchinova IA, Flower DR: VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinforma 2007, 8:4. BioMed Central Full Text
• [17]Vivona S, Bernante F, Filippini F: NERVE: new enhanced reverse vaccinology environment. BMC Biotechnol 2006, 6:35. BioMed Central Full Text
• [18]He Y, Xiang Z, Mobley HL: Vaxign: the first web-based vaccine design program for reverse vaccinology and applications for vaccine development. J Biomed Biotechnol 2010, 2010:297505.
• [19]Wizemann TM, Adamou JE, Langermann S: Adhesins as targets for vaccine development. Emerg Infect Dis 1999, 5:395-403.
• [20]Cao J, Gong Y, Cai B, Feng W, Wu Y, Li L, Zou Y, Ying B, Wang L: Modulation of human bronchial epithelial cells by pneumococcal choline binding protein A. Hum Immunol 2011, 72:37-46.
• [21]Zou L, Wang J, Huang B, Xie M, Li A: A solute-binding protein for iron transport in Streptococcus iniae. BMC Microbiol 2010, 10:309. BioMed Central Full Text
• [22]Easton DM, Smith A, Gallego SG, Foxwell AR, Cripps AW, Kyd JM: Characterization of a novel porin protein from Moraxella catarrhalis and identification of an immunodominant surface loop. J Bacteriol 2005, 187:6528-6535.
• [23]Turbyfill KR, Kaminski RW, Oaks EV: Immunogenicity and efficacy of highly purified invasin complex vaccine from Shigella flexneri 2a. Vaccine 2008, 26:1353-1364.
• [24]Schorey JS, Holsti MA, Ratliff TL, Allen PM, Brown EJ: Characterization of the fibronectin-attachment protein of Mycobacterium avium reveals a fibronectin-binding motif conserved among mycobacteria. Mol Microbiol 1996, 21:321-329.
• [25]Potter AA, Schryvers AB, Ogunnariwo JA, Hutchins WA, Lo RY, Watts T: Protective capacity of the Pasteurella haemolytica transferrin-binding proteins TbpA and TbpB in cattle. Microb Pathog 1999, 27:197-206.
• [26]Tang C, Holden D: Pathogen virulence genes–implications for vaccines and drug therapy. Br Med Bull 1999, 55:387-400.
• [27]Zarantonelli ML, Antignac A, Lancellotti M, Guiyoule A, Alonso JM, Taha MK: Immunogenicity of meningococcal PBP2 during natural infection and protective activity of anti-PBP2 antibodies against meningococcal bacteraemia in mice. J Antimicrob Chemother 2006, 57:924-9230.
• [28]Chen YS, Hsiao YS, Lin HH, Yen CM, Chen SC, Chen YL: Immunogenicity and anti-Burkholderia pseudomallei activity in Balb/c mice immunized with plasmid DNA encoding flagellin. Vaccine 2006, 24:750-758.
• [29]Tong HH, Li D, Chen S, Long JP, DeMaria TF: Immunization with recombinant Streptococcus pneumoniae neuraminidase NanA protects chinchillas against nasopharyngeal colonization. Infect Immun 2005, 73:7775-7778.
• [30]Ko J, Splitter GA: Molecular host-pathogen interaction in brucellosis: current understanding and future approaches to vaccine development for mice and humans. Clin Microbiol Rev 2003, 16:65-78.
• [31]Rappuoli R, Pizza M, Douce G, Dougan G: New vaccines against bacterial toxins. Adv Exp Med Biol 1996, 397:55-60.
• [32]Palumbo RN, Wang C: Bacterial invasin: structure, function, and implication for targeted oral gene delivery. Curr Drug Deliv 2006, 3:47-53.
• [33]Achouak W, Heulin T, Pagès JM: Multiple facets of bacterial porins. FEMS Microbiol Lett 2001, 199:1-7.
• [34]Ramos HC, Rumbo M, Sirard JC: Bacterial flagellins: mediators of pathogenicity and host immune responses in mucosa. Trends Microbiol 2004, 12:509-17.
• [35]Galán JE: Bacterial toxins and the immune system: show me the in vivo targets. J Exp Med 2005, 201:321-323.
• [36]Henderson B, Nair S, Pallas J, Williams MA: Fibronectin: a multidomain host adhesin targeted by bacterial fibronectin-binding proteins. FEMS Microbiol Rev 2011, 35:147-200.
• [37]Ratledge C, Dover LG: Iron metabolism in pathogenic bacteria. Annu Rev Microbiol 2000, 54:881-941.
• [38]Sauvage E, Kerff F, Terrak M, Ayala JA, Charlier P: The penicillin-binding proteins: structure and role in peptidoglycan biosynthesis. FEMS Microbiol Rev 2008, 32:234-258.
• [39]Rosenow C, Ryan P, Weiser JN, Johnson S, Fontan P, Ortqvist A, Masure HR: Contribution of novel choline-binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae. Mol Microbiol 1997, 25:819-29.
• [40]Yu NY, Wagner JR, Laird MR, Melli G, Rey S, Lo R, Dao P, Sahinalp SC, Ester M, Foster LJ, Brinkman FS: PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes. Bioinformatics 2010, 26:1608-1615.
• [41]Tusnády GE, Simon I: The HMMTOP transmembrane topology prediction server. Bioinformatics 2001, 17:849-850.
• [42]Punta M, Coggill PC, Eberhardt RY, Mistry J, Tate J, Boursnell C, Pang N, Forslund K, Ceric G, Clements J, Heger A, Holm L, Sonnhammer EL, Eddy SR, Bateman A, Finn RD: The Pfam protein families database. Nucleic Acids Res 2012, 40(Database issue):D290-301.
• [43]Vita R, Zarebski L, Greenbaum JA, Emami H, Hoof I, Salimi N, Damle R, Sette A, Peters B: The immune epitope database 2.0. Nucleic Acids Res 2010, 38(Database issue):D854-862.
• [44]Iwai LK, Juliano MA, Juliano L, Kalil J, Cunha-Neto E: T-cell molecular mimicry in Chagas disease: identification and partial structural analysis of multiple cross-reactive epitopes between Trypanosoma cruzi B13 and cardiac myosin heavy chain. J Autoimmun 2005, 24:111-117.
• [45]Grossman Z, Paul WE: Autoreactivity, dynamic tuning and selectivity. Curr Opin Immunol 2001, 13:687-698.
• [46]Yang B, Sayers S, Xiang Z, He Y: Protegen: a web-based protective antigen database and analysis system. Nucleic Acids Res 2011, 39(Database issue):D1073-1078.
• [47]Giefing C, Meinke AL, Hanner M, Henics T, Bui MD, Gelbmann D, Lundberg U, Senn BM, Schunn M, Habel A, Henriques-Normark B, Ortqvist A, Kalin M, von Gabain A, Nagy E: Discovery of a novel class of highly conserved vaccine antigens using genomic scale antigenic fingerprinting of pneumococcus with human antibodies. J Exp Med 2008, 205:117-1131.
• [48]Talkington DF, Brown BG, Tharpe JA, Koenig A, Russell H: Protection of mice against fatal pneumococcal challenge by immunization with pneumococcal surface adhesin A (PsaA). Microb Pathog 1996, 21:17-22.
• [49]Garmory HS, Titball RW: ATP-binding cassette transporters are targets for the development of antibacterial vaccines and therapies. Infect Immun 2004, 72:6757-6763.
• [50]Sadilkova L, Nepereny J, Vrzal V, Sebo P, Osicka R: Type IV fimbrial subunit protein ApfA contributes to protection against porcine pleuropneumonia. Vet Res 2012, 43:2. BioMed Central Full Text
• [51]Lee JS, Shin SJ, Collins MT, Jung ID, Jeong YI, Lee CM, Shin YK, Kim D, Park YM: Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein activates dendritic cells and induces a Th1 polarization. Infect Immun 2009, 77:2979-2988.
• [52]Nobbs AH, Lamont RJ, Jenkinson HF: Streptococcus adherence and colonization. Microbiol Mol Biol Rev 2009, 73:407-450.
• [53]Loosmore SM, Yang YP, Oomen R, Shortreed JM, Coleman DC, Klein MH: The Haemophilus influenzae HtrA protein is a protective antigen. Infect Immun 1998, 66:899-906.
• [54]Hagan EC, Mobley HL: Uropathogenic Escherichia coli outer membrane antigens expressed during urinary tract infection. Infect Immun 2007, 75:3941-3949.
• [55]Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, et al.: Initial sequencing and analysis of the human genome. Nature 2001, 409:860-921.
• [56]Del Val M, Schlicht HJ, Volkmer H, Messerle M, Reddehase MJ, Koszinowski UH: Protection against lethal cytomegalovirus infection by a recombinant vaccine containing a single nonameric T-cell epitope. J Virol 1991, 65:3641-3646.
• [57]Fiers MW, Kleter GA, Nijland H, Peijnenburg AA, Nap JP, van Ham RC: Allermatch, a webtool for the prediction of potential allergenicity according to current FAO/WHO Codex alimentarius guidelines. BMC Bioinforma 2004, 5:133. BioMed Central Full Text