A new design and epitopes analysis for recombinant vaccine against Salmonella typhi by In silico analysis

Tahereh Bidmeshki Barzoki, Ali Mohammad Ahadi, Hoda Ayat


Nowadays, foodborne diseases are one of the main problems in the world that infect humans due to consumption of contaminated water or food. Typhoid fever is one of the major causes of illness and death in the world caused by Salmonella typhi. Vaccination is one of the most effective approaches in order to reducing the risk of disease. The main goal of this study is designing and characterization of antigenic determinants of a fusion protein originated from S.typhi usable as an effective vaccine. In this study, the outer membrane proteins of salmonella have been considered as candidates conferring protection against typhoid. Considering the evidence, OmpA, OmpF and OmpC proteins of salmonella applied in a multivalent vaccine design. Conserved motives of these proteins were selected using the CLC software and then their extracellular regions of these peptides were identified with PRED-TMBB server. Appropriate motives were combined for design of final fusion protein. Finally epitops of designed protein with high antigenic properties were identified using BCPREDS, Ellipro, ABCpred, EpiJen, NetCTL-1.2, CTLpred, TAPpred, ProPred and VaxiJen servers. Predicted designed protein in this study reached a very high scores for antigenic indexes. Encoding Genetic construction of this fusion protein could be applied for production of the recombinant OmpA.OmpF.OmpC derived fusion protein with effective antigenic properties as a new vaccine against S. typhi. Laboratory experiments and animal challenging analyses is ongoing.



Salmonella typhi; recombinant;multiepitopic; vaccine

Full Text:



Nosrat S, Sabokbar A, Dezfoolian M, Tabarraie B, Fallah F: Prevalence of Salmonella enteritidis, typhi and typhimurium from food products in Mofid hospital. Research in Medicine 2012, 36(1):43-48.

Crump JA, Luby SP, Mintz ED: The global burden of typhoid fever. Bulletin of the World Health Organization 2004, 82:346-353.

Butler T,Treatment of typhoid fever in the 21st century: promises and shortcomings. Clinical Microbiology and Infection 2011, 17:959-963. Doi: 10.1111/j.1469-0691.2011.03552.x.

Guzman CA, Borsutzky S, Griot-Wenk M, Metcalfe IC, Pearman J, Collioud A, Favre D, Dietrich G: Vaccines against typhoid fever. Vaccine 2006, 24:3804-3811. Doi: 10.1016/j.vaccine.2005.07.111.

Dougan G, John V, Palmer S, Mastroeni P: Immunity to salmonellosis. Immunological reviews 2011, 240:196-210. Doi: 10.1111/j.1600-065X.2010.00999.x.

Garmory HS, Brown KA, Titball RW: Salmonella vaccines for use in humans: present and future perspectives. FEMS microbiology reviews 2002, 26:339-353.

Fraser A, Goldberg E, Acosta CJ, Paul M, Leibovici L: Vaccines for preventing typhoid fever. Cochrane Database Syst Rev 200718;(3):CD001261. Doi: 10.1002/14651858.CD001261.pub2.

Bhutta ZA, Khan MI, Soofi SB, Ochiai RL: New advances in typhoid Fever vaccination strategies. Adv Exp Med Biol. 2011;697:17-39. Doi: 10.1007/978-1-4419-7185-2_3.

Toobak H, Rasooli I, Talei D, Jahangiri A, Owlia P, Astaneh SDA: Immune response variations to Salmonella enterica serovar Typhi recombinant porin proteins in mice. Biologicals 2013, 41(4):224-230. Doi: 10.1016/j.biologicals.2013.05.005.

Dougan G, Baker S: Salmonella enterica serovar Typhi and the pathogenesis of typhoid fever. Annual review of microbiology 2014, 68:317-336. Doi: 10.1146/annurev-micro-091313-103739.

Kaljee LM, Denise AP, Deepak G, Kshitu B, Imran Khan K. Social and Economic Burden Associated With Typhoid Fever in Kathmandu and Surrounding Areas: A Qualitative Study . Journal of Infectious Diseases, 2017;s1-s7. Doi.org/10.1093/infdis/jix122.

Dekker J, Frank K. Salmonella, Shigella, and Yersinia. Clin Lab Med.2015;35(2): 225–246. Doi: 10.1016/j.cll.2015.02.002

Kaur J, Jain S: Role of antigens and virulence factors of Salmonella enterica serovar Typhi in its pathogenesis. Microbiological research 2012, 167(4):199-210. doi: 10.1016/j.micres.2011.08.001.

Sabbagh SC, Forest CG, Lepage C, Leclerc JM, Daigle F: So similar, yet so different: uncovering distinctive features in the genomes of Salmonella enterica serovars Typhimurium and Typhi. FEMS microbiology letters 2010, 305(1):1-13. doi: 10.1111/j.1574-6968.2010.01904.x.

Wiedemann A, Virlogeux-Payant I, Chaussé A-M, Schikora A, Velge P: Interactions of Salmonella with animals and plants. Frontiers in Microbiology 2015, 5:791. doi: 10.3389/fmicb.2014.00791.

Bhat NH, Jain S: Immunogenic evaluation of a recombinant 49-kilodalton outer membrane protein of Salmonella typhi as a candidate for a subunit vaccine against typhoid. Journal of Infectious Diseases and Immunity 2010, 2:30-40.

Ranjbar R, Izadi M, Joneydi Jafari N, Panahi Y: The accuracy rate of laboratory reports of typhoid fever. MilMed Journal 2010, 12:149-152.

Ochiai RL, Acosta CJ, Danovaro-Holliday M, Baiqing D, Bhattacharya SK, Agtini MD, Bhutta ZA, Canh DG, Ali M, Shin S: A study of typhoid fever in five Asian countries: disease burden and implications for controls. Bulletin of the World Health Organization 2008, 86:260-268. doi: 10.2471/BLT.06.039818.

Isibasi A, Ortiz V, Vargas M, Paniagua J, Gonzalez C, Moreno J, Kumate J: Protection against Salmonella typhi infection in mice after immunization with outer membrane proteins isolated from Salmonella typhi 9, 12, d, Vi. Infection and immunity 1988, 56:2953-2959.

Begum F, Adachi Y, Khan M: Immunological characterization of 37.81 KDA common immunodominant surface protein of some Salmonella serovars. Bangladesh Journal of Veterinary Medicine 2008, 6:145-151. Doi: http://dx.doi.org/10.3329/bjvm.v11i1.17732.

Arockiasamy A, Krishnaswamy S: Purification of integral outer-membrane protein OmpC, a surface antigen from Salmonella typhi for structure–function studies: a method applicable to enterobacterial major outer-membrane protein. Analytical Biochemistry 2000, 283:64-70. Doi: 10.1006/abio.2000.4634.

Kumar VS, Gautam V, Balakrishna K, Kumar S: Overexpression, purification, and immunogenicity of recombinant porin proteins of Salmonella enterica Serovar Typhi (S. Typhi). J Microbiol Biotechnol 2009, 19(9):1034-40.

Huber VJ, Tsujita M, Nakada T: Aquaporins in drug discovery and pharmacotherapy. Molecular aspects of medicine 2012, 33:691-703. Doi: 10.1016/j.mam.2012.01.002.

Bagos PG, Liakopoulos TD, Spyropoulos IC, Hamodrakas SJ: PRED-TMBB: a web server for predicting the topology of β-barrel outer membrane proteins. Nucleic acids research 2004, 32:W400-W404. Doi: 10.1093/nar/gkh417.

Kelley LA, Sternberg MJ: Protein structure prediction on the Web: a case study using the Phyre server. Nature protocols 2009, 4:363-371. Doi: 10.1038/nprot.2009.2

Rost B, Yachdav G, Liu J: The predictprotein server. Nucleic acids research 2004, 32:W321-W326. Doi: 10.1093/nar/gkh377.

McGuffin LJ, Bryson K, Jones DT: The PSIPRED protein structure prediction server. Bioinformatics 2000, 16:404-405.

Biosciences Y: YASARA: Yet another scientific artificial reality application. 2010.

Doytchinova IA, Flower DR: VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC bioinformatics 2007, 8:4. Doi: 10.1186/1471-2105-8-4

Ponomarenko J, Bui H-H, Li W, Fusseder N, Bourne PE, Sette A, Peters B: ElliPro: a new structure-based tool for the prediction of antibody epitopes. BMC bioinformatics 2008, 9:514. Doi: 10.1186/1471-2105-9-514.

Saha S, Raghava G: ABCPred benchmarking datasets. 2006a. 2008.

Doytchinova IA, Guan P, Flower DR: EpiJen: a server for multistep T cell epitope prediction. BMC bioinformatics 2006;7:131. Doi:10.1186/1471-2105-7-131

Lundegaard C, Lund O, Nielsen M: Prediction of epitopes using neural network based methods. Journal of immunological methods 2011, 374:26-34. Doi: 10.1016/j.jim.2010.10.011.

Bhasin M, Raghava G: Prediction of CTL epitopes using QM, SVM and ANN techniques. Vaccine 2004, 22:3195-3204. Doi: 10.1016/j.vaccine.2004.02.005.

Bhasin M, Raghava G: Analysis and prediction of affinity of TAP binding peptides using cascade SVM. Protein Science 2004, 13:596-607. Doi: 10.1110/ps.03373104.

Singh H, Raghava G: ProPred: prediction of HLA-DR binding sites. Bioinformatics 2001, 17:1236-1237.

Marathe SA, Lahiri A, Negi VD, Chakravortty D: Typhoid fever & vaccine development: a partially answered question. The Indian journal of medical research 2012, 135:161.

MacLennan CA, Martin LB, Micoli F: Vaccines against invasive Salmonella disease: current status and future directions. Human vaccines & immunotherapeutics 2014, 10:1478-1493. Doi: 10.4161/hv.29054.

Jafarpour, S., Ayat, H., Ahadi AM: Design and Antigenic Epitopes Prediction of a New Trial Recombinant Multiepitopic Rotaviral Vaccine: In Silico Analyses. Viral Immunol 2015, 28(6):325-30. Doi: 10.1089/vim.2014.0152.

Verdugo-Rodriguez A, Gam L-H, Oevl S, Koh C, Puthucheary S, Calva E, Pang T: Detection of Antibodies against Salmonella typhiOuter Membrane Protein (OMP) Preparation in Typhoid Fever Patients. Asian Pacific Journal of Allergy and Immunology 1993, 11(1):45-52.

Rosa DS, Ribeiro SP, Cunha-Neto E: CD4+ T cell epitope discovery and rational vaccine design. Archivum immunologiae et therapiae experimentalis 2010, 58(2):121-130. Doi: 10.1007/s00005-010-0067-0

DOI: http://dx.doi.org/10.24294/ti.v2.i4.891


  • There are currently no refbacks.

Copyright (c) 2018 Tahereh Bidmeshki Barzoki, Ali Mohammad Ahadi, Hoda Ayat

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Creative Commons License

This site is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.