Original Article
 

In Silico Design and Evaluation of Acinetobacter baumannii Outer Membrane Protein A (OmpA) Antigenic Peptides As Vaccine Candidate in Immunized Mice

Abstract

Acinetobacter baumannii is a Gram-negative bacterium that has recently been identified as a leading nosocomial pathogen. Infections by this pathogen result in significant mortality due to antibiotic resistance. An effective vaccine would help alleviate the burden of disease incurred by this pathogen; however, there are currently no licensed vaccines offering protection against Acinetobacter baumannii infection. In this study, considering the fact that outer membrane protein A is one of the most promising vaccine candidates, we predicted T cell and B cell epitopes on this protein using sequence-based epitope prediction tools and determined whether or not mice immunized with these peptides induce an immune response. We selected consensus epitopes including five peptides in different tools with the highest score. 48 female C5BL/6 SPF injected subcutaneously with the peptides (peptide1 to peptide 5 separately) in 100 μL of the solution and sham groups received adjuvant and PBS alone on the same schedule: on day 0 (primary dose) and two booster doses were administered on days 14 and 28. At the end of time, animals euthanized by Isoflurane, and collected sera for assessment of specific antibodies against each peptide by ELISA (Enzyme-linked immunosorbent assay). Immunization of mice showed one of the novel synthetic peptides (peptide 1 (24-50 amino acids)) elicited immune responses. We conclude to combine theoretical methods of epitope prediction and evaluating the potential of immunogenicity for developing vaccines is important.

1. Tarek A. Ahmad AB, Dina M, Tawfik BC, Salah, et al. Development of immunization trials against Acinetobacter baumannii. Trials in Vaccinology 2016; 5:53–60
2. Noori E, Rasooli I, Owlia P, Mousavi Gargari SL, Ebrahimizadeh W. A conserved region from biofilm associated protein as a biomarker for detection of Acinetobacter baumannii. Microb Pathog 2014;77:84–8.
3. 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.
4. Luo G, Lin L, Ibrahim AS, Baquir B, Pantapalangkoor P, Bonomo RA, et al. Active and passive immunization protects against lethal, extreme drug resistant-Acinetobacter baumannii infection. PLoS ONE 2012;7(1):e29446.
5. Mortensen BL, Skaar EP. Host-microbe interactions that shape the pathogenesis of Acinetobacter baumannii infection. Cell Microbiol 2012;14(9):1336–44.
6. Chen W. Current advances and challenges in the development of Acinetobacter vaccines. Hum Vaccin Immunother 2015;11(10):2495–500.
7. Tarek A.Ahmad Amrou E. Eweida. Salah A.Sheweita" B-cell epitope mapping for the design of vaccines and effective diagnostics". Trials in Vaccinology 2016; 5:71-83.
8. Farhadi T, Nezafat N, Ghasemi Y, Karimi Z, Hemmati S, Erfani N. Designing of Complex Multi-epitope Peptide Vaccine Based on Omps of Klebsiella pneumoniae: An In Silico Approach. International Journal of Peptide Researsh and Therapeutics 2015: 21(3):325-41.
9. Nafarieh T, Bandehpour M, Hashemi A, Taheri S, Yardel V, Jamaati H, et al. Identification of antigens from nosocomial Acinetobacter baumannii clinical isolates in sera from ICU staff and infected patients using the antigenome technique. World J Microbiol Biotechnol 2017;33(10):189.
10. Rahbar MR, Rasooli I, Gargari SLM, Sandstrom G, Amani J, Fattahian Y, et al. A potential in silico antibody–antigen based diagnostic test for precise identification of Acinetobacter baumannii. J Theor Biol 2012;294:29–39.
11. Roy A, Kucukural A, Zhang Y. I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc 2010;5(4):725–38.
12. Zhang Y. Template-based modeling and free modeling by I-TASSER in CASP7. Proteins 2007;69(S8):108–17.
13. Laskowski RA, MacArthur MW, Moss DS and Thornton JM. PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Cryst 1993; 26:283-91.
14. Singh H, Ansari HR, Raghava GP. Improved method for linear B-cell epitope prediction using antigen's primary sequence. PLoS One 2013; 8(5).
15. Yao B, Zhang L, Liang S, Zhang C. SVMTriP: A Method to Predict Antigenic Epitopes Using Support Vector Machine to Integrate Tri-Peptide Similarity and Propensity. Porollo A, editor. PLoS ONE;7(9):e45152.
16. Saha S, Raghava GPS. Prediction of continuous B-cell epitopes in an antigen using recurrent neural network. Proteins 2006;65(1):40–8.
17. Sudipto Saha, Gajendra PS. Raghava BcePred. Prediction of Continuous B-Cell Epitopes in Antigenic Sequences Using Physico-chemical Properties: Artificial Immune Systems 2004:197-204.
18. El-manzalawy Y, Dobbs D, Honavar V. Predicting linear B-cell epitopes using string kernels. J Mol Recognit2008; 21(4):243–55.
19. Ansari HR, Raghava GPS. Identification of conformational B-cell Epitopes in an antigen from its primary sequence. Immun Res2010;6(1):6.
20. Nithichanon A, Rinchai D, Gori A, Lassaux P. Sequence- and Structure-Based Immunoreactive Epitope Discovery for Burkholderia pseudomallei Flagellin. PLoS Negl Trop Dis2015; 9(7):e0003917.
21. Thomas S, Thirumalapura NR, Crocquet-Valdes PA, Luxon BA, Walker DH. Structure-Based Vaccines Provide Protection in a Mouse Model of Ehrlichiosis. PLoS One2011;6(11):e27981.
22. Gourlay LJ, Peri C, Ferrer-Navarro M, Conchillo-Solé O, Gori A, Rinchai D, et al. Exploiting the Burkholderia pseudomallei Acute Phase Antigen BPSL2765 for Structure-Based Epitope Discovery/Design in Structural Vaccinology. Chem Biol 2013;20(9):1147–56.
23. Li W, Joshi MD, Singhania S, Ramsey KH, Murthy AK. Peptide Vaccine: Progress and Challenges. Vaccines (Basel) 2014; 2(3):515–36.
24. Hailemichael Y, Overwijk WW. Peptide-based anticancer vaccines. OncoImmunology 2013;2(7):e24743.
25. Croft NP, Purcell AW. Peptidomimetics: modifying peptides in the pursuit of better vaccines. Expert Rev Vaccines 2011;10(2):211–26.
26. Akarsu H, Iwatsuki-Horimoto K, Noda T, Kawakami E, Katsura H, Baudin F, et al. Structure-based design of NS2 mutants for attenuated influenza A virus vaccines. Virus Res 2011;155(1):240–8.
27. Wang TT, Tan GS, Hai R, Pica N, Ngai L, Ekiert DC, et al. Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes. Proc Natl Acad Sci U S A 2010;107(44):18979–84.
28. Nazarian S, Mousavi Gargari SL, Rasooli I, Amani J, Bagheri S, Alerasool M. An in silico chimeric multi subunit vaccine targeting virulence factors of enterotoxigenic Escherichia coli (ETEC) with its bacterial inbuilt adjuvant. J Microbiol Methods 2012;90(1):36–45.
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IssueVol 18, No 6 (2019) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijaai.v18i6.2178
PMID32245309
Keywords
Acetinobacter baumannii Antigenic peptide In silico Outer membrane protein A (OmpA) Vaccine

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How to Cite
1.
Mehdinejadiani K, Bandehpour M, Hashemi A, Ranjbar MM, Taheri S, Jalali SA, Mosaffa N. In Silico Design and Evaluation of Acinetobacter baumannii Outer Membrane Protein A (OmpA) Antigenic Peptides As Vaccine Candidate in Immunized Mice. Iran J Allergy Asthma Immunol. 2019;18(6):655-663.