Screening of HLA class II epitope-based peptides as potential vaccine candidates is one of the most rational approach for vaccine development against Hendra virus (HeV) infection, for which currently there is no successful vaccine in practice. In this study, screening of epitopes from HeV proteins viz matrix, glycoprotein, nucleocapsid, fusion, C protein, V protein, W protein and polymerase, followed by highest binding affinity & molecular dynamic simulation of selected T-cell epitopes with their corresponding HLA class II alleles has been done. The server ProPred facilitates the binding prediction of HLA class II allele specific epitopes from the antigenic protein sequences of HeV. PEPstrMOD server was used for PDB structure modeling of the screened epitopes and MODELLER was used for HLA alleles modeling. We docked the selected T-cell epitopes with their corresponding HLA allele structures using the AutoDock 4.2 tool. Further the selected docked complex structures were optimized by NAnoscale Molecular Dynamics program (NAMD) at 5 ps, with the CHARMM-22 force field parameter incorporated in Visual Molecular Dynamics (VMD 1.9.2) and complex structure stability was evaluated by calculating RMSD values. Epitopes IRIFVPATN (Nucleocapsid), MRNLLSQSL (Nucleocapsid), VRRAGKYYS (Matrix) and VRLKCLLCG (Fusion) proteins have shown considerable binding with DRB1*0806, DRB1*1304, DRB1*0701 and DRB1*0301 HLA class II allele respectively. Toxicity, antigenicity and population coverage of epitopes IRIFVPATN, MRNLLSQSL, VRRAGKYYS and VRLKCLLCG were analyzed by Toxin Pred, Vexijen and IEDB tool, respectively. The potential T-cell epitopes can be utilized in designing comprehensive epitope-based vaccines and diagnostic kits against Hendra virus after further in-vivo studies.
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Despite considerable efforts, a suitable vaccine against Onchocerca volvulus infection has remained elusive. Herein, we report on the use of molecular tools to identify and characterize O. volvulus antigens that are possibly associated with the development of concomitant immunity in onchocerciasis.Methodology/Principal Findings
Third-stage larvae (L3) and molting L3 (mL3) O. volvulus stage-specific cDNA libraries were screened with a pool of sera from chronically infected patients who had likely developed such immunity. The 87 immunoreactive clones isolated were grouped into 20 distinct proteins of which 12 had already been cloned and/or characterized before and 4 had been proven to be protective in a small O. volvulus animal model. One of these, onchocystatin (Ov-CPI-2), a previously characterized O. volvulus cysteine proteinase inhibitor was, overall, the most abundant clone recognized by the immune sera in both the L3 and mL3 cDNA libraries. To further characterize its association with protective immunity, we measured the IgG subclass and IgE class specific responses to the antigen in putatively immune (PI) and infected (INF) individuals living in a hyperendemic area in Cameroon. It appeared that both groups had similar IgG3 and IgE responses to the antigen, but the INF had significantly higher IgG1 and IgG4 responses than the PI individuals (p<0.05). In the INF group, the IgG3 levels increased significantly with the age of the infected individuals (r = 0.241; p<0.01). The IgG1 responses in the INF were high regardless of age. Notably, culturing L3 in vitro in the presence of anti-Ov-CPI-2 monospecific human antibodies and naïve neutrophils resulted in almost complete inhibition of molting of L3 to L4 and to cytotoxicity to the larvae.Conclusions/Significance
These results add to the knowledge of protective immunity in onchocerciasis and support the possible involvement of anti-Ov-CPI-2 IgG1 and/or IgG3 cytophilic antibodies in the development of protective immunity in the PI and the INF. The results further support the consideration of Ov-CPI-2 as a leading target for an anti-L3 vaccine. 相似文献Teschovirus A belongs to the family Picornaviridae and is a causal agent of the disease Teschovirus encephalomyelitis and other infections that remain asymptomatic. The present study was performed to design epitope-based peptide vaccine against Teschovirus A by identifying the potential T cell and B-cell epitopes from capsid proteins (VP1, VP3 and VP2) of the virus using reverse vaccinology and immunoinformatics approaches. In the current study, hexapeptide T-cell and octapeptide B-cell epitopes were analyzed for immunogenicity, antigenicity and hydrophilicity scores of each epitope. Each potential epitope was further characterized using ExPASy-ProtParam and Antimicrobial Peptide Database (APD3) tools for determining various physical and chemical parameters of the epitope. One linear hexapeptide T-cell epitope, i.e., RPVNDE (epitope position 77–82) and one linear octapeptide B-cell epitope, i.e., AYSRSHPQ (236–243) were identified from the viral capsid protein as they possess the capability to raise effective immunogenic reaction in the host organism against the virus. Pharmaceutical industries could harness the results of this investigation to develop epitope-based peptide vaccines by loading the identified epitopes in combination with targeting signal peptides of T-cells and B-cells and then inserting the combination into virus like particle (vlp) or constructing subunit vaccines for further trial.
相似文献Hepatitis C virus (HCV) infection is a major global issue that leads to serious liver disease such as chronic liver inflammation and hepatocellular carcinoma. At present, no approved vaccine is available for control or treatment of HCV infection. Therefore, the development of an efficient vaccine against HCV is an urgent need. Today, designing an effective vaccine against hepatitis C is one of the outmost propriety for researchers. Fusion protein vaccines containing the immunogen proteins and adjuvant molecules are able to stimulate both humoral and cellular responses that are crucial for eradicating HCV infection. Herein, in silico design of fusion forms of vaccine candidates against HCV, including flagellin (fliC) from Pseudomonas aeruginosa and NS5B antigen (NT300) from HCV was performed. First, two forms of fusion protein (NT300-fliC and fliC-NT300) were designed and analyzed using different bioinformatics tools. For this aim, the Iterative threading assembly refinement (I-TASSER) server was used for modeling the fusion forms of protein; namely, NT300-fliC and fliC-NT300, then the high-rank 3D model of fusion protein was selected, subsequently various physico-chemical, and structural parameters were examined bioinformatically. After the selection of the best construct (fliC-NT300), the interaction of flagellin part of vaccine with toll-like receptor 5 (TLR5) was evaluated via docking studies. Our results represented that based on data obtained from various servers, and the docking analyses of two constructs, fliC-NT300 fusion form showed better results than NT300-fliC. For this reason, the fliC-NT300 form was selected for further evaluations. In sum, structural and immunological computational studies showed that the fliC-NT300 can be introduced as a prophylactic or therapeutic candidate vaccine against the HCV, after the efficacy of that was confirmed via in vitro and in vivo assays.
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