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Original article

Vol. 149 No. 2324 (2019)

Design and evaluation of a multi-epitope assembly peptide vaccine against Acinetobacter baumannii infection in mice

  • Shan Ren
  • Lina Guan
  • Yao Dong
  • Chaoli Wang
  • Li Feng
  • Yongen Xie
Cite this as:
Swiss Med Wkly. 2019;149:w20052
Published
16.06.2019

Summary

AIM

To design a multi-epitope assembly peptide (MEP) of Acinetobacter baumannii and evaluate its immunogenicity and protective immunity in Balb/c mice.

METHODS

The T- and B-cell epitopes of outer membrane proteins FilF and NucAb from A. baumannii were predicted and identified by using bioinformatics software and immunological tests. Peptides with predicted high adhesin probability from A. baumannii Ata protein was used as the backbone, two B-cell epitopes and one CD4+ T-cell epitope from FilF were linked to the N-terminal of the backbone, and two B-cell epitopes and one CD4+ T-cell epitope from NucAb were linked to the C-terminal of the backbone to construct the MEP. The gene of the MEP was expressed in E. coli BL21, and its immunogenicity and protective efficacy were evaluated in Balb/c mice.

RESULTS

A recombinant protein with a molecular weight of about 37 kDa was successfully purified, and was identified as the recombinant multi-epitope assembly peptide (rMEP) by Western blot analysis. The animal tests showed that the rMEP was highly immunogenic and could induce high levels of IgG antibody and provide potent protection (88.9%) against lethal doses of A. baumannii.

CONCLUSIONS

This is the first report of the design and study of a rMEP vaccine against A. baumannii. The results indicate that the rMEP is a promising vaccine candidate for the control of infections caused by A. baumannii.

References

  1. Garnacho J, Sole-Violan J, Sa-Borges M, Diaz E, Rello J. Clinical impact of pneumonia caused by Acinetobacter baumannii in intubated patients: a matched cohort study. Crit Care Med. 2003;31(10):2478–82. doi:.https://doi.org/10.1097/01.CCM.0000089936.09573.F3
  2. Kim SW, Choi CH, Moon DC, Jin JS, Lee JH, Shin JH, et al. Serum resistance of Acinetobacter baumannii through the binding of factor H to outer membrane proteins. FEMS Microbiol Lett. 2009;301(2):224–31. doi:.https://doi.org/10.1111/j.1574-6968.2009.01820.x
  3. Dijkshoorn L, Nemec A, Seifert H. An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii. Nat Rev Microbiol. 2007;5(12):939–51. doi:.https://doi.org/10.1038/nrmicro1789
  4. McConnell MJ, Rumbo C, Bou G, Pachón J. Outer membrane vesicles as an acellular vaccine against Acinetobacter baumannii. Vaccine. 2011;29(34):5705–10. doi:.https://doi.org/10.1016/j.vaccine.2011.06.001
  5. Lin L, Tan B, Pantapalangkoor P, Ho T, Hujer AM, Taracila MA, et al. Acinetobacter baumannii rOmpA vaccine dose alters immune polarization and immunodominant epitopes. Vaccine. 2013;31(2):313–8. doi:.https://doi.org/10.1016/j.vaccine.2012.11.008
  6. Sefidi MD, Rasooli I, Owlia P, Talei D, Astaneh SD, Nazarian S. Adjuvant role of Pseudomonas flagellin for Acinetobacter baumannii biofilm associated protein. World J Methodol. 2016;6(3):190–9. doi:.https://doi.org/10.5662/wjm.v6.i3.190
  7. Huang W, Wang S, Yao Y, Xia Y, Yang X, Long Q, et al. OmpW is a potential target for eliciting protective immunity against Acinetobacter baumannii infections. Vaccine. 2015;33(36):4479–85. doi:.https://doi.org/10.1016/j.vaccine.2015.07.031
  8. Chiang MH, Sung WC, Lien SP, Chen YZ, Lo AF, Huang JH, et al. Identification of novel vaccine candidates against Acinetobacter baumannii using reverse vaccinology. Hum Vaccin Immunother. 2015;11(4):1065–73. doi:.https://doi.org/10.1080/21645515.2015.1010910
  9. Perez F, Bonomo RA. Vaccines for Acinetobacter baumannii: thinking “out of the box”. Vaccine. 2014;32(22):2537–9. doi:.https://doi.org/10.1016/j.vaccine.2014.03.031
  10. Yang W, Jackson DC, Zeng Q, McManus DP. Multi-epitope schistosome vaccine candidates tested for protective immunogenicity in mice. Vaccine. 2000;19(1):103–13. doi:.https://doi.org/10.1016/S0264-410X(00)00165-1
  11. Xu Q, Ma X, Wang F, Li H, Zhao X. Evaluation of a multi-epitope subunit vaccine against avian leukosis virus subgroup J in chickens. Virus Res. 2015;210:62–8. doi:.https://doi.org/10.1016/j.virusres.2015.06.024
  12. Singh R, Garg N, Shukla G, Capalash N, Sharma P. Immunoprotective efficacy of Acinetobacter baumannii outer membrane protein, FilF, predicted in silico as a potential vaccine candidate. Front Microbiol. 2016;7:158. doi:.https://doi.org/10.3389/fmicb.2016.00158
  13. Garg N, Singh R, Shukla G, Capalash N, Sharma P. Immunoprotective potential of in silico predicted Acinetobacter baumannii outer membrane nuclease, NucAb. Int J Med Microbiol. 2016;306(1):1–9. doi:.https://doi.org/10.1016/j.ijmm.2015.10.005
  14. Bentancor LV, Routray A, Bozkurt-Guzel C, Camacho-Peiro A, Pier GB, Maira-Litrán T. Evaluation of the trimeric autotransporter Ata as a vaccine candidate against Acinetobacter baumannii infections. Infect Immun. 2012;80(10):3381–8. doi:.https://doi.org/10.1128/IAI.06096-11
  15. Larsen JE, Lund O, Nielsen M. Improved method for predicting linear B-cell epitopes. Immunome Res. 2006;2(1):2. doi:.https://doi.org/10.1186/1745-7580-2-2
  16. Saha S, Raghava GP. Prediction of continuous B-cell epitopes in an antigen using recurrent neural network. Proteins. 2006;65(1):40–8. doi:.https://doi.org/10.1002/prot.21078
  17. Nielsen M, Lund O, Buus S, Lundegaard C. MHC class II epitope predictive algorithms. Immunology. 2010;130(3):319–28. doi:.https://doi.org/10.1111/j.1365-2567.2010.03268.x
  18. Reche PA, Glutting JP, Zhang H, Reinherz EL. Enhancement to the RANKPEP resource for the prediction of peptide binding to MHC molecules using profiles. Immunogenetics. 2004;56(6):405–19. doi:.https://doi.org/10.1007/s00251-004-0709-7
  19. 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. doi:.https://doi.org/10.1155/2010/297505
  20. García-Quintanilla M, Pulido MR, Pachón J, McConnell MJ. Immunization with lipopolysaccharide-deficient whole cells provides protective immunity in an experimental mouse model of Acinetobacter baumannii infection. PLoS One. 2014;9(12):e114410. doi:.https://doi.org/10.1371/journal.pone.0114410
  21. Huang W, Wang S, Yao Y, Xia Y, Yang X, Li K, et al. Employing Escherichia coli-derived outer membrane vesicles as an antigen delivery platform elicits protective immunity against Acinetobacter baumannii infection. Sci Rep. 2016;6(1):37242. doi:.https://doi.org/10.1038/srep37242
  22. McConnell MJ, Domínguez-Herrera J, Smani Y, López-Rojas R, Docobo-Pérez F, Pachón J. Vaccination with outer membrane complexes elicits rapid protective immunity to multidrug-resistant Acinetobacter baumannii. Infect Immun. 2011;79(1):518–26. doi:.https://doi.org/10.1128/IAI.00741-10
  23. Lin L, Tan B, Pantapalangkoor P, Ho T, Hujer AM, Taracila MA, et al. Acinetobacter baumannii rOmpA vaccine dose alters immune polarization and immunodominant epitopes. Vaccine. 2013;31(2):313–8. doi:.https://doi.org/10.1016/j.vaccine.2012.11.008
  24. McConnell MJ, Pachón J. Active and passive immunization against Acinetobacter baumannii using an inactivated whole cell vaccine. Vaccine. 2010;29(1):1–5. doi:.https://doi.org/10.1016/j.vaccine.2010.10.052
  25. McConnell MJ, Rumbo C, Bou G, Pachón J. Outer membrane vesicles as an acellular vaccine against Acinetobacter baumannii. Vaccine. 2011;29(34):5705–10. doi:.https://doi.org/10.1016/j.vaccine.2011.06.001
  26. Moriel DG, Beatson SA, Wurpel DJ, Lipman J, Nimmo GR, Paterson DL, et al. Identification of novel vaccine candidates against multidrug-resistant Acinetobacter baumannii. PLoS One. 2013;8(10):e77631. doi:.https://doi.org/10.1371/journal.pone.0077631
  27. Ahmad TA, Tawfik DM, Sheweita SA, Haroun M, El-Sayed LH. Development of immunization trials against Acinetobacter baumannii. Trials Vaccinol. 2016;5:53–60. doi:.https://doi.org/10.1016/j.trivac.2016.03.001
  28. Garcia-Quintanilla M, Pulido MR, McConnell MJ. First steps towards a vaccine against Acinetobacter baumannii. Curr Pharm Biotechnol. 2013;14(10):897–902. doi:.https://doi.org/10.2174/1389201014666131226123511
  29. Guo SJ, Ren S, Xie YE. Evaluation of the protective efficacy of a fused OmpK/Omp22 protein vaccine candidate against Acinetobacter baumannii infection in mice. Biomed Environ Sci. 2018;31(2):155–8.
  30. Chen W. Current advances and challenges in the development of Acinetobacter vaccines. Hum Vaccin Immunother. 2015;11(10):2495–500. doi:.https://doi.org/10.1080/21645515.2015.1052354
  31. Sette A, Rappuoli R. Reverse vaccinology: developing vaccines in the era of genomics. Immunity. 2010;33(4):530–41. doi:.https://doi.org/10.1016/j.immuni.2010.09.017
  32. Hosseingholi EZ, Rasooli I, Gargari SL. In silico analysis of Acinetobacter baumannii phospholipase D as a subunit vaccine candidate. Acta Biotheor. 2014;62(4):455–78. doi:.https://doi.org/10.1007/s10441-014-9226-8
  33. Russo TA, Beanan JM, Olson R, MacDonald U, Luke NR, Gill SR, et al. Rat pneumonia and soft-tissue infection models for the study of Acinetobacter baumannii biology. Infect Immun. 2008;76(8):3577–86. doi:.https://doi.org/10.1128/IAI.00269-08
  34. Bist P, Dikshit N, Koh TH, Mortellaro A, Tan TT, Sukumaran B. The Nod1, Nod2, and Rip2 axis contributes to host immune defense against intracellular Acinetobacter baumannii infection. Infect Immun. 2014;82(3):1112–22. doi:.https://doi.org/10.1128/IAI.01459-13
  35. García-Patiño MG, García-Contreras R, Licona-Limón P. The immune response against Acinetobacter baumannii, an emerging pathogen in nosocomial infections. Front Immunol. 2017;8:441. doi:.https://doi.org/10.3389/fimmu.2017.00441