A new approach toward cancer therapy is the use of cancer vaccine, yet the different molecular bases of cancers, reduce the effectiveness of this approach. In this article, we aim to use matrix metalloproteinase-9 protein (MMP9) which is an essential molecule in the survival and metastasis of all types of cancers as a target for universal cancer vaccine design. The reference sequence of MMP9 protein was obtained from NCBI databases. Furthermore, the B-cell and T cell-related peptides were analyzed using the IEDB website and other related soft wares. The best candidate peptides were then visualized using chimera software. Three peptides were found to be good candidates for interactions with B cells (SLPE, RLYT, and PALPR), while 10 peptides were found as good targets for interactions with MHC1 and another 10 peptides founded suitable for interactions with MHC2 with population coverages of 94.77 and 90.67%, respectively. Finally, the immune response simulation and molecular docking were done using the C-IMMSIM simulator and AutoDock Vina to confirm the effectiveness of the proposed vaccine. By the end of this project: twenty-three peptide-based vaccine was designed for use as a universal cancer vaccine which has a high world population coverage for MHC1 (94.77%) and MHC2 (90.67%) related alleles.
Burkitt's lymphoma (BL) is an aggressive form of non-Hodgkin lymphoma, originates from germinal center B cells, MYC gene (MIM ID 190080) is an important proto-oncogene transcriptional factor encoding a nuclear phosphoprotein for central cellular processes. Dysregulated expression or function of c-MYC is one of the most common abnormalities in BL. This study focused on the investigation of the possible role of single nucleotide polymorphisms (SNPs) in MYC gene associated with formation of BL.MYC SNPs were obtained from NCBI database. SNPs in the coding region that are nonsynonymous (nsSNPs) were analysed by multiple programs such as SIFT, Polyphen2, SNPs&GO, PHD-SNP and I-mutant. In this study, a total of 286 Homo sapiens SNPs were found. Roughly, forty-eight of them were deleterious and were furtherly investigated. Eight SNPs were considered most disease causing [rs4645959 (N26S), rs4645959 (N25S), rs141095253 (P396L), rs141095253 (P397L), rs150308400 (C233Y), rs150308400 (C147Y), rs150308400 (C147Y), rs150308400 (C148Y)] according to the four softwares used. Two of which have not been reported previously [rs4645959 (N25S), rs141095253 (P396L)]. SNPs analysis helps is a diagnostic marker which helps in diagnosing and consequently, finding therapeutics for clinical diseases. This is through SNPs genotyping arrays and other techniques. Thus, it is highly recommended to confirm the findings in this study in vivo and in vitro.
The fungus Candida albicans is an opportunistic pathogen that causes a wide range of infections. It's the primary cause of candidiasis and the fourth most common cause of nosocomial infection. In addition, disseminated invasive candidiasis which is a major complication of the disease has an estimated mortality rate of 40%-60% even with the use of antifungal drugs. Over the last decades, several different anti-Candida vaccines have been suggested with different strategies for immunization against candidiasis such as, live-attenuated fungi, recombinant proteins, and glycoconjugates but none has been approved by the FDA, yet. This study aims to introduce a new possible vaccine for C. albicans through analyzing peptides of its pyruvate kinase (PK) protein as an immunogenic stimulant computationally.A total number of 28 C. albicans, pyruvate kinase proteins were obtained from NCBI on the 9 th of February 2019 and were subjected to multiple sequence alignment using Bioedit for conservancy. The main analytical tool was IEDB, Chimera for homology modelling, and MOE for docking.Among the tested peptides, fifteen promising T-cell peptides were predicted. Five peptides were more important than the others (HMIFASFIR, YRGVYPFIY, AVAAVSAAY, LRWAVSEAV, and IFASFIRTA) They show high Binding Affinity to MHC molecules, low binding energy required indicating more stable bonds, and their ideal length of nine peptides. (PTRAEVSDV) peptide is the most promising linear B-cell peptide due to its physiochemical parameters and optimal length (nine amino acids). It's highly recommended to have these five strong candidates in future in vivo and in vitro analysis studies.Keywords: candida albicans, immunoinformatics, multi-epitope, peptide-based vaccine, pyruvate kinase, vaccine design Non-linear B-cell epitopes 1.3.2.1 ElliPro Antibody epitopes prediction:It's a tool that works using the PDB ID of the protein, providing minimum score of (0.5) and maximum distance of (6) to predict non-linear peptides. It provides 3D model of the clustered peptides with the result. 42 (available at: http://tools.iedb.org/ellipro/) T-cell epitopes prediction:1.4.2 Binding to MHC class I prediction tool:
Objective: European bat lyssaviruses (EBLV) type 2 is present in many European countries. Infection is usually seen in bats, the primary reservoirs of the viruses. Human deaths have been documented within few days following bat exposures. So, it is very useful to design an insilco peptide vaccine for European bat lyssaviruses type 2 virus using glycoprotein G as an immunogen to stimulate protective immune response. Results: B cell tests were conducted for Bepipred with 15 conserved epitopes, Emini surface accessibility prediction with 7 conserved epitopes in the surface and Kolaskar and Tongaonkar antigenicity tested with three conserved epitopes being antigenic. 357 conserved epitopes were predicted to interact with different MHC-1 alleles with (IC50) ≤500 while 282 conserved epitopes found to interact with MHC-II alleles with IC50≤ 1000. Among all tested epitopes for world population coverage the epitope VFSYMELKV binding to MHC11 alleles was 97.94% and it found to bind 10 different alleles that indicate strong potential to formulate peptide vaccine for lyssaviruses type 2 virus. To the best of our knowledge this is the first study to propose peptide vaccine for European bat lyssavirus type 2.
BackgroundLymphocyte enhancer factor-1 (LEF-1) is a member of the LEF-1/TCF family of transcription factors that are critically involved in canonical Wnt/β-catenin Signaling to regulate B Lymphocyte proliferation and survival. Alteration of LEF1 expression and function leads to leukemogenesis as well as other several neoplasms.Aimsto identify mutations in exons two and three of the LEF1 among B-CLL Sudanese patients. Also, to functionally analyze the detected SNPs using different in silico tools.Materials and methodsImmuno-phenotype for the detection of B cells CD5 and CD19 markers was performed on 128 B-CLL Sudanese patients by using a flow cytometry technique. DNA extraction, conventional PCR, and Sanger sequencing were applied to the LEF1 gene. Also, we performed a mutational analysis for identified SNPs using bioinformatics tools.ResultsA positive CD5 & CD19 expression was found in B-CLL patients. No mutation was observed in exon two. While four mutations were observed in exon three; two of them were not reported in previous studies. Interestingly, splicing analysis predicted that these mutations could lead to splicing defects in LEF1 pre-mRNA due to their potential effects on splicing regulatory elements (i.e. ESE).Conclusionthe two mutations Pro134Pro and Ile135Asn (novel mutation) were detected in all enrolled CLL patients and they could be used as diagnostic and/or prognostic markers for CLL. Therefore, further in vitro and in vivo functional studies with a large sample size are required to verify the splicing effect of the detected mutations in LEF1 pre-mRNA.
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