Abstract:Background
Influenza A virus is one of the leading causes of annual mortality. The emerging of novel escape variants of the influenza A virus is still a considerable challenge in the annual process of vaccine production. The evolution of vaccines ranks among the most critical successes in medicine and has eradicated numerous infectious diseases. Recently, multi-epitope vaccines, which are based on the selection of epitopes, have been increasingly investigated.
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“…As a result, CTxB has been widely employed as an adjuvant in vaccine design to boost immune responses [ 108 – 110 ]. In this study, like many other studies, the AAY linker was used to connect CTL epitopes [ 85 , 111 , 112 ], the GGGGS linker to connect HTL epitopes [ 113 , 114 ], the KK linker to connect LBL epitopes [ 115 – 117 ], and the EAAAK linker to connect adjuvant [ 116 , 118 , 119 ]. The AAY linkers help to increase epitope presentation while decreasing the formation of junctional epitopes [ 120 ].…”
Monkeypox virus (MPXV) outbreaks have been reported in various countries worldwide; however, there is no specific vaccine against MPXV. In this study, therefore, we employed computational approaches to design a multi-epitope vaccine against MPXV. Initially, cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), linear B lymphocytes (LBL) epitopes were predicted from the cell surface-binding protein and envelope protein A28 homolog, both of which play essential roles in MPXV pathogenesis. All of the predicted epitopes were evaluated using key parameters. A total of 7 CTL, 4 HTL, and 5 LBL epitopes were chosen and combined with appropriate linkers and adjuvant to construct a multi-epitope vaccine. The CTL and HTL epitopes of the vaccine construct cover 95.57% of the worldwide population. The designed vaccine construct was found to be highly antigenic, non-allergenic, soluble, and to have acceptable physicochemical properties. The 3D structure of the vaccine and its potential interaction with Toll-Like receptor-4 (TLR4) were predicted. Molecular dynamics (MD) simulation confirmed the vaccine’s high stability in complex with TLR4. Finally, codon adaptation and in silico cloning confirmed the high expression rate of the vaccine constructs in strain K12 of Escherichia coli (E. coli). These findings are very encouraging; however, in vitro and animal studies are needed to ensure the potency and safety of this vaccine candidate.
“…As a result, CTxB has been widely employed as an adjuvant in vaccine design to boost immune responses [ 108 – 110 ]. In this study, like many other studies, the AAY linker was used to connect CTL epitopes [ 85 , 111 , 112 ], the GGGGS linker to connect HTL epitopes [ 113 , 114 ], the KK linker to connect LBL epitopes [ 115 – 117 ], and the EAAAK linker to connect adjuvant [ 116 , 118 , 119 ]. The AAY linkers help to increase epitope presentation while decreasing the formation of junctional epitopes [ 120 ].…”
Monkeypox virus (MPXV) outbreaks have been reported in various countries worldwide; however, there is no specific vaccine against MPXV. In this study, therefore, we employed computational approaches to design a multi-epitope vaccine against MPXV. Initially, cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), linear B lymphocytes (LBL) epitopes were predicted from the cell surface-binding protein and envelope protein A28 homolog, both of which play essential roles in MPXV pathogenesis. All of the predicted epitopes were evaluated using key parameters. A total of 7 CTL, 4 HTL, and 5 LBL epitopes were chosen and combined with appropriate linkers and adjuvant to construct a multi-epitope vaccine. The CTL and HTL epitopes of the vaccine construct cover 95.57% of the worldwide population. The designed vaccine construct was found to be highly antigenic, non-allergenic, soluble, and to have acceptable physicochemical properties. The 3D structure of the vaccine and its potential interaction with Toll-Like receptor-4 (TLR4) were predicted. Molecular dynamics (MD) simulation confirmed the vaccine’s high stability in complex with TLR4. Finally, codon adaptation and in silico cloning confirmed the high expression rate of the vaccine constructs in strain K12 of Escherichia coli (E. coli). These findings are very encouraging; however, in vitro and animal studies are needed to ensure the potency and safety of this vaccine candidate.
“…String of CTL epitopes was inserted along with an AAY linker between five individual CTL epitopes. It was predicted that the AAY linkers could significantly improve the expression of certain target proteins and enhance the immunogenicity of a multi-epitope influenza vaccine designed in silico for the production in E. coli [ 53 ]. However, the sequence to be inserted may affect the solubility and VLP-forming ability of chimeric HBc VLPs [ 54 ].…”
Virus-like particles (VLPs) offer an attractive possibility for the development of vaccines. Recombinant core antigen (HBc) of Hepatitis B virus (HBV) was expressed in different systems, and the E. coli expression system was shown to be effective for the production of HBc VLPs. Here, we used HBc of the HBV genotype G (HBc/G) as a technologically promising VLP carrier for the presentation of spike RBM and nucleocapsid protein-derived peptides of the SARS-CoV-2 Delta variant for subsequent immunological evaluations of obtained fusion proteins. The major immunodominant region (MIR) of the HBc/G protein was modified through the insertion of a receptor binding motif (RBM) from the S protein or B-cell epitope-containing peptide from the N protein. The C-terminus of the two truncated HBc/G proteins was used for the insertion of a group of five cytotoxic T lymphocyte (CTL) epitopes from the N protein. After expression in E. coli, the MIR-derived proteins were found to be insoluble and were recovered through step-wise solubilization with urea, followed by refolding. Despite the lack of correct VLPs, the chimeric proteins induced high levels of antibodies in BALB/c mice. These antibodies specifically recognized either eukaryotically expressed hRBD or bacterially expressed N protein (2–220) of SARS-CoV-2. CTL-epitope-containing proteins were purified as VLPs. The production of cytokines was analyzed through flow cytometry after stimulation of T-cells with target CTL peptides. Only a protein with a deleted polyarginine (PA) domain was able to induce the specific activation of T-cells. At the same time, the T-cell response against the carrier HBc/G protein was detected for both proteins. The neutralization of SARS-CoV-2 pseudotyped murine retrovirus with anti-HBc/G-RBM sera was found to be low.
“…The simulator is built on a state-of-the-art agent-based model which describes the RRMS patient in terms of (i) a complete, multifunctional description of the immune system, (ii) a disease-specific RRMS extension, and (iii) an easily extensible treatment module. The multifunctional base model has been deployed to describe a variety of immune-related pathologies and vaccines [26] , [27] , [28] . The model includes a detailed description of both innate and adaptive immune system, such as different cell types, key immune system processes, cytokines and chemokines signaling.…”
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