Background. Respiratory syncytial virus (RSV) infection is a public health epidemic, leading to around 3 million hospitalization and about 66,000 deaths each year. It is a life-threatening condition exclusive to children with no effective treatment. Methods. In this study, we used system-level and vaccinomics approaches to design a polyvalent vaccine for RSV, which could stimulate the immune components of the host to manage this infection. Our framework involves data accession, antigenicity and subcellular localization analysis, T cell epitope prediction, proteasomal and conservancy evaluation, host-pathogen-protein interactions, pathway studies, and in silico binding affinity analysis. Results. We found glycoprotein (G), fusion protein (F), and small hydrophobic protein (SH) of RSV as potential vaccine candidates. Of these proteins (G, F, and SH), we found 9 epitopes for multiple alleles of MHC classes I and II bear significant binding affinity. These potential epitopes were linked to form a polyvalent construct using AAY, GPGPG linkers, and cholera toxin B adjuvant at N-terminal with a 23.9 kDa molecular weight of 224 amino acid residues. The final construct was a stable, immunogenic, and nonallergenic protein containing cleavage sites, TAP transport efficiency, posttranslation shifts, and CTL epitopes. The molecular docking indicated the optimum binding affinity of RSV polyvalent construct with MHC molecules (-12.49 and -10.48 kcal/mol for MHC classes I and II, respectively). This interaction showed that a polyvalent construct could manage and control this disease. Conclusion. Our vaccinomics and system-level investigation could be appropriate to trigger the host immune system to prevent RSV infection.

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Background. Liver cancer (LC) is the most devastating disease affecting a large set of populations in the world. The mortality due to LC is escalating, indicating the lack of effective therapeutic options. Immunotherapeutic agents may play an important role against cancer cells. As immune cells, especially T lymphocytes, which are part of cancer immunology, the design of vaccine candidates for cytotoxic T lymphocytes may be an effective strategy for curing liver cancer. Results. In our study, based on an immunoinformatics approach, we predicted potential T cell epitopes of MHC class I molecules using integrated steps of data retrieval, screening of antigenic proteins, functional analysis, peptide synthesis, and experimental in vivo investigations. We predicted the binding affinity of epitopes LLECADDRADLAKY, VSEHRIQDKDGLFY, and EYILSLEELVNGMY of LC membrane-bounded extracellular proteins including butyrophilin-like protein-2 (BTNL2), glypican-3 (GPC3), and serum albumin (ALB), respectively, with MHC class I molecules (allele: HLA-A ∗ 01:01). These T cell epitopes rely on the level of their binding energy and antigenic properties. We designed and constructed a trivalent immunogenic model by conjugating these epitopes with linkers to activate cytotoxic T cells. For validation, the nonspecific hematological assays showed a significant rise in the count of white blood cells ( 5 × 10 9 / l ), lymphocytes ( 13 × 10 9 / l ), and granulocytes ( 5 × 10 9 / l ) compared to the control after administration of trivalent peptides. Specific immunoassays including granzyme B and IgG ELISA exhibited the significant concentration of these effector molecules in blood serum, indicating the activity of cytotoxic T cells. Granzyme concentration increased to 1050 pg/ml at the second booster dose compared to the control (95 pg/ml), while the concentration of IgG raised to 6 g/l compared to the control (2 g/l). Conclusion. We concluded that a potential therapeutic trivalent vaccine can activate and modulate the immune system to cure liver cancer on the basis of significant outcomes of specific and nonspecific assays.

Type 2 diabetes mellitus (T2DM) is the most prevailing worldwide health challenge of the 21st century and the 5th leading cause of death worldwide. About 90% of diabetic patients are diagnosed as having T2DM. LPAR1 gene codes LPA protein that is involved in the regulation of many biological processes. In this study, we have investigated the association of single nucleotide polymorphism (SNP) of LPAR1 gene variants rs494605 and rs558347 with T2DM in our local population. This association was analyzed by amplification of the target gene through Tetra ARMS PCR. The study involved 200 participants with equal ration of cases and controls. Both genetic variants of LPAR1 rs494605 and rs558347 have allelic origin T/C. The allelic frequency of LPAR1 was calculated through the Hardy Weinberg Equilibrium. re found that in LPAR1 rs494605 mutant allele, C was 47% in cases compared to controls (39%) and in LPAR1 rs558347, heterozygosity allele (TC) was 46% compared to mutant allele C (13%), while wild T allele was 17% in cases. Many demographic and lifestyle risk factors were significantly associated with LPAR1 gene variants. The heterogeneity of genetic variants with T2DM also showed a strong correlation with obesity, hormonal imbalance, and depression with p-value of 0.001, and 95% confidence interval. Smoking and alcohol consumption are major risk factors of T2DM. Variations in LPAR1 can be used as a biomarker and diagnostic tool for T2DM.

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