The Construction of A Multi-epitope Vaccine Against Klebsiella pneumoniae Using in silico Approach

Dhammiko Wonggo, Mariana Wahjudi

Abstract


Background: Klebsiella pneumoniae is one of the bacteria that causes pneumonia infection. Even though the number of pneumonia cases is relatively high and has become a global problem, there is still no vaccine available to prevent this disease. This study was aimed to design a multi-epitope vaccine design through an in silico approach, against K. pneumoniae.

Materials and method: Vaccine candidate was constructed based on proteins of K. pneumoniae. These proteins were analyzed to identify the antigens sequence for multi-epitope vaccine design. The constructed vaccine was predicted for allergenicity, toxicity, population coverage, and its physicochemical properties. The vaccine structure was then docked with the toll like receptor 2 (TLR2) molecule to show the interaction. Expression analysis and cloning of the constructed vaccine was carried out in the pET-28a vector using SnapGene.

Results: The vaccine was 567 amino acids long, consisting of Cholera Toxin Subunit B as an adjuvant, 6 B-cell epitopes, 11 cytotoxic T-cell epitopes, and 10 helper T-cell epitopes connected with the appropriate linker. Epitopes analysis showed that the vaccine will be a non-toxic, has high antigenicity, but non-allergenic. The vaccine was predicted to be stable, hydrophilic, and had a low risk of triggering autoimmune response. The vaccine molecule was compatible to humans TLR2 molecule. Furthermore, visualization of the candidate vaccine protein on pET-28a showed that the vaccine protein might be expressed correctly.

Conclusion: The construction of multi-epitope vaccine has been developed, which might be a good vaccine candidate, containing 6 B-cell epitopes, 11 CTL epitopes, and 10 HTL epitopes. The construct may help scientists to experimentally formulate multi-epitope vaccine against K. pneumoniae in the future.

Keywords: in silico, Klebsiella pneumoniae, multi-epitope, vaccine

 


Full Text:

PDF

References


Ali S, Alam M, Hasan GM, Hassan MI. Potential therapeutic targets of Klebsiella pneumoniae: a multi-omics review perspective. Brief Funct Genomics. 2022; 21(2): 63-77, CrossRef.

Puspitasari D, Rusli EA, Husada D, Kartina L. Escherichia coli and Klebsiella pneumonia as the most common bacteria causing catheter associated urinary tract infection. Mol Cell Biomed Sci. 2021; 5(3): 121-6, CrossRef.

Dey J, Mahapatra SR, Lata S, Patro S, Misra N, Suar M. Exploring Klebsiella pneumoniae capsule polysaccharide proteins to design multiepitope subunit vaccine to fight against pneumonia. Expert Rev Vaccines. 2022; 21(4): 569-87, CrossRef.

Dharmawan A, Karuniawati A, Sudarmono PP, Lestari DC, Rumende CM. Epithelial cells count and the ratio of leukocytes and epithelial cells as the criteria to determine qualified specimen for community-acquired pneumonia (CAP)-causing pathogens identification. Indones Biomed J. 2020; 12(1): 34-9, CrossRef.

Zargaran FN, Akya A, Rezaeian S, Ghadiri K, Lorestani RC, Madanchi H, et al. B cell epitopes of four fimbriae antigens of Klebsiella pneumoniae: A comprehensive in silico study for vaccine development. Int J Pept Res Ther. 2021; 27(2): 875-86, CrossRef.

Mahapatra SR, Dey J, Kaur T, Sarangi R, Bajoria AA, Kushwaha GS, et al. Immunoinformatics and molecular docking studies reveal a novel Multi-Epitope peptide vaccine against pneumonia infection. Vaccine. 2021; 39(42): 6221-37, CrossRef.

Jalal K, Khan K, Basharat Z, Abbas MN, Uddin R, Ali F, et al. Reverse vaccinology approach for multi-epitope centered vaccine design against delta variant of the SARS-CoV-2. Environ Sci Pollut Res. 2022; 29(40): 60035-53, CrossRef.

Swetha RG, Basu S, Ramaiah S, Anbarasu A. Multi-epitope vaccine for monkeypox using pan-genome and reverse vaccinology approaches. Viruses. 2022; 14(11): 2504, CrossRef.

Purwanti R, Indrati AR, Suraya N, Montain MM, Atmosukarto I, Nurainy N, et al. ESAT-6-Ag85C-polyHistag antigen fusion is potential as vaccine candidate for tuberculosis. Indones Biomed J. 2023; 15(2): 165-70, CrossRef.

Lundberg U, Senn BM, Schüler W, Meinke A, Hanner M. Identification and characterization of antigens as vaccine candidates against Klebsiella pneumoniae. Hum Vaccin Immunother. 2013; 9(3): 497-505, CrossRef.

Tandirogang N, Fitriany E, Mardania N, Jannah M, Dilan BFN, Ratri SR, et al. Neutralizing antibody response by inactivated SARS-CoV-2 vaccine on healthcare workers. Mol Cell Biomed Sci. 2023; 7(1): 18-27, CrossRef.

Aslam S, Ashfaq UA, Zia T, Aslam N, Alrumaihi F, Shahid F, et al. Proteome based mapping and reverse vaccinology techniques to contrive multi-epitope based subunit vaccine (MEBSV) against Streptococcus pyogenes. Infect Genet Evol. 2022; 100: 105259, CrossRef.

Shabani NRM, Ismail CMKH, Leow CH, Mokhtar M, Singh KKB, Leow CY. Identification of MHC class II immunopeptidomes from Shigella flexneri 2a-infected macrophages as potential vaccine candidates. Indones Biomed J. 2022; 14(2): 139-47, CrossRef.

Anggini PW, Amanina SA, Asyura SR, Dion R. In silico study of essential oil of Bambusa vulgaris leaves as an anti beta-lactamase compound. Mol Cell Biomed Sci. 2022; 6(3): 147-54, CrossRef.

Li L, Yu T, Ma Y, Yang Z, Wang W, Song X, et al. The genetic structures of an extensively drug resistant (XDR) Klebsiella pneumoniae and its plasmids. Front Cell Infect Microbiol. 2018; 8: 446, CrossRef.

Van Regenmortel MHV. What is a b-cell epitope? Methods Mol Biol. 2009; 524: 3-20, CrossRef.

Kalita P, Padhi AK, Zhang KYJ, Tripathi T. Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2. Microb Pathog. 2020; 145: 104236, CrossRef.

Stewart E, Triccas JA, Petrovsky N. Adjuvant strategies for more effective tuberculosis vaccine immunity. Microorganisms. 2019; 7(8): 255, CrossRef.

Stratmann T. Cholera toxin subunit B as adjuvant--An accelerator in protective immunity and a break in autoimmunity. Vaccines. 2015; 3(3): 579-96, CrossRef.

Rajendran Krishnamoorthy H, Karuppasamy R. Designing a novel SOX9 based multi-epitope vaccine to combat metastatic triple-negative breast cancer using immunoinformatics approach. Mol Divers. 2022; 2022: 1-14, CrossRef.

Ayyagari VS, Venkateswarulu TC, Abraham Peele K, Srirama K. Design of a multi-epitope-based vaccine targeting M-protein of SARS-CoV2: an immunoinformatics approach. J Biomol Struct Dyn. 2022; 40(7): 2963-77, CrossRef.

Oluwagbemi OO, Oladipo EK, Dairo EO, Ayeni AE, Irewolede BA, Jimah EM, et al. Computational construction of a glycoprotein multi-epitope subunit vaccine candidate for old and new South-African SARS-CoV-2 virus strains. Inform Med Unlocked. 2022; 28: 100845, CrossRef.

Gul S, Ahmad S, Ullah A, Ismail S, Khurram M, Tahir Ul Qamar M, et al. Designing a recombinant vaccine against Providencia rettgeri using immunoinformatics approach. Vaccines. 2022; 10(2): 189, CrossRef.

Girija ASS, Shoba G, Priyadharsini JV. Accessing the T-cell and B-cell immuno-dominant peptides from A. baumannii biofilm associated protein (bap) as vaccine candidates: A computational Approach. Int J Pept Res Ther. 2021; 27(1): 37-45, CrossRef.

Dar HA, Ismail S, Waheed Y, Ahmad S, Jamil Z, Aziz H, Hetta HF, Muhammad K. Designing a multi-epitope vaccine against Mycobacteroides abscessus by pangenome-reverse vaccinology. Sci Rep. 2021; 11(1): 11197, CrossRef.

Salaikumaran MR, Kasamuthu PS, Aathmanathan VS, Burra VLSP. An in silico approach to study the role of epitope order in the multi-epitope-based peptide (MEBP) vaccine design. Sci Rep. 2022; 12(1): 12584, CrossRef.

Pandey RK, Bhatt TK, Prajapati VK. Novel immunoinformatics approaches to design multi-epitope subunit vaccine for malaria by investigating anopheles salivary protein. Sci Rep. 2018; 8(1): 1125, CrossRef.




DOI: https://doi.org/10.21705/mcbs.v7i2.343

Copyright (c) 2023 Cell and BioPharmaceutical Institute

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

Indexed by:

               

                      


Cell and BioPharmaceutical Institute