Immunoinformatics design and synthesis of a multi-epitope vaccine against Helicobacter pylori based on lipid nanoparticles.
Helicobacter pylori
/ immunology
Nanoparticles
/ chemistry
Bacterial Vaccines
/ immunology
Computational Biology
/ methods
Humans
Bacterial Proteins
/ immunology
Epitopes
/ immunology
Molecular Docking Simulation
Antigens, Bacterial
/ immunology
Helicobacter Infections
/ prevention & control
Toll-Like Receptor 4
/ immunology
Urease
/ immunology
Immunoinformatics
Liposomes
Helicobacter pylori
Immunoinformatics
Multi-epitope
Vaccine
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 Aug 2024
02 Aug 2024
Historique:
received:
23
02
2024
accepted:
30
07
2024
medline:
3
8
2024
pubmed:
3
8
2024
entrez:
2
8
2024
Statut:
epublish
Résumé
Helicobacter pylori (H. pylori) is responsible for various chronic or acute diseases, such as stomach ulcers, dyspepsia, peptic ulcers, gastroesophageal reflux, gastritis, lymphoma, and stomach cancers. Although specific drugs are available to treat the bacterium's harmful effects, there is an urgent need to develop a preventive or therapeutic vaccine. Therefore, the current study aims to create a multi-epitope vaccine against H. pylori using lipid nanoparticles. Five epitopes from five target proteins of H. pylori, namely, Urease, CagA, HopE, SabA, and BabA, were used. Immunogenicity, MHC (Major Histocompatibility Complex) bonding, allergenicity, toxicity, physicochemical analysis, and global population coverage of the entire epitopes and final construct were carefully examined. The study involved using various bioinformatic web tools to accomplish the following tasks: modeling the three-dimensional structure of a set of epitopes and the final construct and docking them with Toll-Like Receptor 4 (TLR4). In the experimental phase, the final multi-epitope construct was synthesized using the solid phase method, and it was then enclosed in lipid nanoparticles. After synthesizing the construct, its loading, average size distribution, and nanoliposome shape were checked using Nanodrop at 280 nm, dynamic light scattering (DLS), and atomic force microscope (AFM). The designed vaccine has been confirmed to be non-toxic and anti-allergic. It can bind with different MHC alleles at a rate of 99.05%. The construct loading was determined to be about 91%, with an average size of 54 nm. Spherical shapes were also observed in the AFM images. Further laboratory tests are necessary to confirm the safety and immunogenicity of the multi-epitope vaccine.
Identifiants
pubmed: 39095538
doi: 10.1038/s41598-024-68947-x
pii: 10.1038/s41598-024-68947-x
doi:
Substances chimiques
Bacterial Vaccines
0
Lipid Nanoparticles
0
Bacterial Proteins
0
Epitopes
0
Antigens, Bacterial
0
Toll-Like Receptor 4
0
cagA protein, Helicobacter pylori
0
Urease
EC 3.5.1.5
Liposomes
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
17910Informations de copyright
© 2024. The Author(s).
Références
Denic, M., Touati, E. & De Reuse, H. Pathogenesis of Helicobacter pylori infection. Helicobacter 25, e12736 (2020).
doi: 10.1111/hel.12736
pubmed: 32918351
Gravina, A. G. et al. Helicobacter pylori and extragastric diseases: A review. World J. Gastroenterol. 24, 3204 (2018).
doi: 10.3748/wjg.v24.i29.3204
pubmed: 30090002
pmcid: 6079286
Malfertheiner, P. et al. Helicobacter pylori infection. Nat. Rev. Dis. Primers. 9, 19 (2023).
doi: 10.1038/s41572-023-00431-8
pubmed: 37081005
Kowada, A. & Asaka, M. Economic and health impacts of Helicobacter pylori eradication strategy for the treatment of peptic ulcer disease: A cost-effectiveness analysis. Helicobacter 27, e12886 (2022).
doi: 10.1111/hel.12886
pubmed: 35343031
pmcid: 9286595
Dos-Santos-Viana, I. et al. Vaccine development against Helicobacter pylori: From ideal antigens to the current landscape. Expert Rev. Vacc. 20, 989–999 (2021).
doi: 10.1080/14760584.2021.1945450
Takahashi-Kanemitsu, A., Knight, C. T. & Hatakeyama, M. Molecular anatomy and pathogenic actions of Helicobacter pylori CagA that underpin gastric carcinogenesis. Cell. Mol. Immunol. 17, 50–63 (2020).
doi: 10.1038/s41423-019-0339-5
pubmed: 31804619
Uberti, A. F. et al. Helicobacter pylori urease: Potential contributions to Alzheimer’s disease. Int. J. Mol. Sci. 23, 3091 (2022).
doi: 10.3390/ijms23063091
pubmed: 35328512
pmcid: 8949269
Kim, J. M. Helicobacter pylori 89–102 (Springer, 2024).
Xu, C., Soyfoo, D. M., Wu, Y. & Xu, S. Virulence of Helicobacter pylori outer membrane proteins: An updated review. Eur. J. Clin. Microbiol. Infect. Dis. 39, 1821–1830 (2020).
doi: 10.1007/s10096-020-03948-y
pubmed: 32557327
pmcid: 7299134
Doohan, D., Rezkitha, Y. A. A., Waskito, L. A., Yamaoka, Y. & Miftahussurur, M. Helicobacter pylori BabA–SabA key roles in the adherence phase: The synergic mechanism for successful colonization and disease development. Toxins 13, 485 (2021).
doi: 10.3390/toxins13070485
pubmed: 34357957
pmcid: 8310295
Kalali, B., Mejías-Luque, R., Javaheri, A. & Gerhard, M. H. pylori virulence factors: Influence on immune system and pathology. Mediat. Inflamm. 2014, 12 (2014).
doi: 10.1155/2014/426309
Sutton, P. & Boag, J. M. Status of vaccine research and development for Helicobacter pylori. Vaccine 37, 7295–7299 (2019).
doi: 10.1016/j.vaccine.2018.01.001
pubmed: 29627231
pmcid: 6892279
Smoot, D. T. How does Helicobacter pylori cause mucosal damage? Direct mechanisms. Gastroenterology 113, S31–S34 (1997).
doi: 10.1016/S0016-5085(97)80008-X
pubmed: 9394757
Zhou, W.-Y. et al. Therapeutic efficacy of a multi-epitope vaccine against Helicobacter pylori infection in BALB/c mice model. Vaccine 27, 5013–5019 (2009).
doi: 10.1016/j.vaccine.2009.05.009
pubmed: 19446591
Meza, B., Ascencio, F., Sierra-Beltrán, A. P., Torres, J. & Angulo, C. A novel design of a multi-antigenic, multistage and multi-epitope vaccine against Helicobacter pylori: An in silico approach. Infect. Genet. Evol. 49, 309–317 (2017).
doi: 10.1016/j.meegid.2017.02.007
pubmed: 28185986
Guo, L. et al. Immunological features and efficacy of a multi-epitope vaccine CTB-UE against H. pylori in BALB/c mice model. Appl. Microbiol. Biotechnol. 98, 3495–3507 (2014).
doi: 10.1007/s00253-013-5408-6
pubmed: 24370888
Nezafat, N., Eslami, M., Negahdaripour, M., Rahbar, M. R. & Ghasemi, Y. Designing an efficient multi-epitope oral vaccine against Helicobacter pylori using immunoinformatics and structural vaccinology approaches. Mol. BioSyst. 13, 699–713 (2017).
doi: 10.1039/C6MB00772D
pubmed: 28194462
Rahman, N., Ajmal, A., Ali, F. & Rastrelli, L. Core proteome mediated therapeutic target mining and multi-epitope vaccine design for Helicobacter pylori. Genomics 112, 3473–3483 (2020).
doi: 10.1016/j.ygeno.2020.06.026
pubmed: 32562830
Jafari, E. & Mahmoodi, S. Design, expression, and purification of a multi-epitope vaccine against Helicobacter pylori based on Melittin as an adjuvant. Microb. Pathogenesis 157, 104970 (2021).
doi: 10.1016/j.micpath.2021.104970
Ru, Z. et al. Immmunoinformatics-based design of a multi-epitope vaccine with CTLA-4 extracellular domain to combat Helicobacter pylori. FASEB J. 36, e22252 (2022).
doi: 10.1096/fj.202101538RR
pubmed: 35294065
Ma, J. et al. A novel design of multi-epitope vaccine against Helicobacter pylori by immunoinformatics approach. Int. J. Peptide Res. Therapeut. 27, 1027–1042 (2021).
doi: 10.1007/s10989-020-10148-x
Khan, M. et al. Immunoinformatics approaches to explore Helicobacter Pylori proteome (Virulence Factors) to design B and T cell multi-epitope subunit vaccine. Sci. Rep. 9, 13321 (2019).
doi: 10.1038/s41598-019-49354-z
pubmed: 31527719
pmcid: 6746805
Wang, B. et al. Immunological response of recombinant H. pylori multi-epitope vaccine with different vaccination strategies. Int. J. Clin. Exp. Pathology 7, 6559 (2014).
Yang, J. et al. Protection against Helicobacter pylori infection in BALB/c mice by oral administration of multi-epitope vaccine of CTB-UreI-UreB. Pathogens Dis. 73, ftv026 (2015).
Ghosh, P. et al. A novel multi-epitopic peptide vaccine candidate against Helicobacter pylori: In-silico identification, design, cloning and validation through molecular dynamics. Int. J. Peptide Res. Therapeut. 27, 1149–1166 (2021).
doi: 10.1007/s10989-020-10157-w
Urrutia-Baca, V. H. et al. Immunoinformatics approach to design a novel epitope-based oral vaccine against Helicobacter pylori. J. Comput. Biol. 26, 1177–1190 (2019).
doi: 10.1089/cmb.2019.0062
pubmed: 31120321
pmcid: 6786345
Guo, L. et al. Immunologic properties and therapeutic efficacy of a multivalent epitope-based vaccine against four Helicobacter pylori adhesins (urease, Lpp20, HpaA, and CagL) in Mongolian gerbils. Helicobacter 22, e12428 (2017).
doi: 10.1111/hel.12428
Dey, J., Mahapatra, S. R., Raj, T. K., Misra, N. & Suar, M. Identification of potential flavonoid compounds as antibacterial therapeutics against Klebsiella pneumoniae infection using structure-based virtual screening and molecular dynamics simulation. Mol. Divers. 2023, 1–18 (2023).
Dey, J. et al. Designing of multi-epitope peptide vaccine against Acinetobacter baumannii through combined immunoinformatics and protein interaction–based approaches. Immunol. Res. 71, 639–662 (2023).
doi: 10.1007/s12026-023-09374-4
pubmed: 37022613
Dey, J. et al. Designing a novel multi-epitope vaccine to evoke a robust immune response against pathogenic multidrug-resistant Enterococcus faecium bacterium. Gut Pathogens 14, 21 (2022).
doi: 10.1186/s13099-022-00495-z
pubmed: 35624464
pmcid: 9137449
Dey, J. et al. Exploring Klebsiella pneumoniae capsule polysaccharide proteins to design multiepitope subunit vaccine to fight against pneumonia. Expert Rev Vacc. 21, 569–587 (2022).
doi: 10.1080/14760584.2022.2021882
Mahapatra, S. R. et al. Immunoinformatics-guided designing of epitope-based subunit vaccine from Pilus assembly protein of Acinetobacter baumannii bacteria. J. Immunol. Methods 508, 113325 (2022).
doi: 10.1016/j.jim.2022.113325
pubmed: 35908655
Mahapatra, S. R., Dey, J., Raj, T. K., Misra, N. & Suar, M. Designing a next-generation multiepitope-based vaccine against Staphylococcus aureus using reverse vaccinology approaches. Pathogens 12, 376 (2023).
doi: 10.3390/pathogens12030376
pubmed: 36986298
pmcid: 10058999
Mahapatra, S. R. et al. The potential of plant-derived secondary metabolites as novel drug candidates against Klebsiella pneumoniae: Molecular docking and simulation investigation. South Afr. J. Botany 149, 789–797 (2022).
doi: 10.1016/j.sajb.2022.04.043
Narang, P. K. et al. Functional annotation and sequence-structure characterization of a hypothetical protein putatively involved in carotenoid biosynthesis in microalgae. South Afr. J. Botany 141, 219–226 (2021).
doi: 10.1016/j.sajb.2021.04.014
Sudeshna-Panda, S. et al. Investigation on structural prediction of pectate lyase enzymes from different microbes and comparative docking studies with pectin: The economical waste from food industry. Geomicrobiol. J. 39, 294–305 (2022).
doi: 10.1080/01490451.2021.1992042
Margreitter, C., Mayrhofer, P., Kunert, R. & Oostenbrink, C. Antibody humanization by molecular dynamics simulations—in-silico guided selection of critical backmutations. J. Mol. Recogn. 29, 266–275 (2016).
doi: 10.1002/jmr.2527