Abstract
Background: Helicobacter pylori infection and its treatment still remain a challenge for human health worldwide. A variety of antibiotics and combination therapies are currently used to treat H. pylori induced ulcers and carcinoma; however, no effective treatment is available to eliminate the pathogen from the body. Additionally, antibiotic resistance is also one of the main reasons for prolonged and persistent infection.
Aims: Until new drugs are available for this infection, vaccinology seems the only alternative opportunity to exploit against H. pylori induced diseases.
Methods: Multiple epitopes prioritized in our previous study have been tested for their possible antigenic combinations, resulting in 169-mer and 183-mer peptide vaccines containing the amino acid sequences of 3 and 4 epitopes respectively, along with adjuvant (Cholera Toxin Subunit B adjuvant at 5’ end) and linkers (GPGPG and EAAAK).
Results: Poly-epitope proteins proposed as potential vaccine candidates against H. pylori include SabA-HP0289-Omp16-VacA (SHOV), VacA-Omp16-HP0289-FecA (VOHF), VacA-Omp16-HP0289- SabA (VOHS), VacA-Omp16-HP0289-BabA (VOHB), VacA-Omp16-HP0289-SabA-FecA (VOHSF), VacA-Omp16-HP0289-SabA-BabA (VOHSB) and VacA-Omp16-HP0289-BabA-SabA (VOHBS). Structures of these poly-epitope peptide vaccines have been modeled and checked for their affinity with HLA alleles and receptors. These proposed poly-epitope vaccine candidates bind efficiently with A2, A3, B7 and DR1 superfamilies of HLA alleles. They can also form stable and significant interactions with Toll-like receptor 2 and Toll-like receptor 4.
Conclusion: Results suggest that these multi-epitopic vaccines can elicit a significant immune response against H. pylori and can be tested further for efficient vaccine development.
Keywords: H. pylori, multi-epitope vaccine, poly-epitope peptide vaccine, HLA allele binding, TLR2 receptor, TLR4 receptor.
Graphical Abstract
[http://dx.doi.org/10.3748/wjg.v20.i18.5283] [PMID: 24833858]
[http://dx.doi.org/10.1007/s12664-015-0535-x] [PMID: 25721770]
[http://dx.doi.org/10.1016/j.vaccine.2009.05.009] [PMID: 19446591]
[http://dx.doi.org/10.2174/1389557013406666] [PMID: 12369968]
[http://dx.doi.org/10.1038/icb.1997.63] [PMID: 9315485]
[http://dx.doi.org/10.1586/14760584.6.4.591] [PMID: 17669012]
[http://dx.doi.org/10.1016/S0952-7915(03)00083-9] [PMID: 12900280]
[http://dx.doi.org/10.1016/j.meegid.2015.03.027] [PMID: 25818402]
[http://dx.doi.org/10.1186/1471-2105-9-62] [PMID: 18226234]
[http://dx.doi.org/10.1186/1471-2105-8-4] [PMID: 17207271]
[http://dx.doi.org/10.1021/ja026939x] [PMID: 12580598]
[http://dx.doi.org/10.1016/j.jtbi.2014.01.018] [PMID: 24512916]
[http://dx.doi.org/10.3390/vaccines3030579] [PMID: 26350596]
[PMID: 24167156]
[http://dx.doi.org/10.1093/bioinformatics/btp386] [PMID: 19549632]
[http://dx.doi.org/10.1385/1-59259-890-0:571]
[http://dx.doi.org/10.1038/nprot.2010.5] [PMID: 20360767]
[http://dx.doi.org/10.1093/nar/gks493] [PMID: 22649060]
[http://dx.doi.org/10.1093/nar/gks376] [PMID: 22564897]
[http://dx.doi.org/10.1016/j.softx.2015.06.001]
[http://dx.doi.org/10.1016/0263-7855(96)00018-5] [PMID: 8744570]
[http://dx.doi.org/10.1006/biol.2001.0297] [PMID: 11851327]
[http://dx.doi.org/10.1073/pnas.93.2.734] [PMID: 8570625]
[http://dx.doi.org/10.1146/annurev.iy.13.040195.003103] [PMID: 7612235]
[http://dx.doi.org/10.1073/pnas.1014708107] [PMID: 21115828]
[http://dx.doi.org/10.1002/jcc.20084] [PMID: 15264254]
[http://dx.doi.org/10.1016/S0968-0004(97)01140-7] [PMID: 9433130]
[http://dx.doi.org/10.1093/nar/gku339] [PMID: 24771341]
[http://dx.doi.org/10.1074/jbc.270.30.17771] [PMID: 7629077]
[http://dx.doi.org/10.1053/j.gastro.2007.06.056] [PMID: 17854597]
[http://dx.doi.org/10.1016/j.canlet.2008.11.016] [PMID: 19111390]
[http://dx.doi.org/10.1073/pnas.96.22.12778] [PMID: 10535999]
[http://dx.doi.org/10.1007/978-1-4899-1382-1_21]
[http://dx.doi.org/10.1128/IAI.00312-12] [PMID: 22566509]
[http://dx.doi.org/10.1016/j.drudis.2008.12.007] [PMID: 19150507]
[http://dx.doi.org/10.1016/j.compbiolchem.2016.04.006] [PMID: 27107181]
[http://dx.doi.org/10.4049/jimmunol.168.11.5499] [PMID: 12023344]
[http://dx.doi.org/10.1126/science.1082305] [PMID: 12690201]
[http://dx.doi.org/10.1038/nm0202-166] [PMID: 11821901]
[http://dx.doi.org/10.2353/ajpath.2008.080142] [PMID: 18583313]
[http://dx.doi.org/10.1016/j.coi.2008.03.007] [PMID: 18440213]
[http://dx.doi.org/10.4049/jimmunol.173.3.1966] [PMID: 15265931]
[http://dx.doi.org/10.1016/S0198-8859(99)00137-8] [PMID: 10717810]
[PMID: 16474276]
[http://dx.doi.org/10.1046/j.1365-2443.2001.00458.x] [PMID: 11554921]