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Design of a Multiepitope Vaccine against Chicken Anemia Virus Disease.

ABSTRACT: Chicken anemia virus (CAV) causes severe clinical and sub-clinical infection in poultry globally and thus leads to economic losses. The drawbacks of the commercially available vaccines against CAV disease signal the need for a novel, safe, and effective vaccine design. In this study, a multiepitope vaccine (MEV) consisting of T-cell and B-cell epitopes from CAV viral proteins (VP1 and VP2) was computationally constructed with the help of linkers and adjuvant. The 3D model of the MEV construct was refined and validated by different online bioinformatics tools. Molecular docking showed stable interaction of the MEV construct with TLR3, and this was confirmed by Molecular Dynamics Simulation. Codon optimization and in silico cloning of the vaccine in pET-28a (+) vector also showed its potential expression in the E. coli K12 system. The immune simulation also indicated the ability of this vaccine to induce an effective immune response against this virus. Although the vaccine in this study was computationally constructed and still requires further in vivo study to confirm its effectiveness, this study marks a very important step towards designing a potential vaccine against CAV disease.

SUBMITTER: Fatoba AJ

PROVIDER: S-EPMC9318905 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Design of a Multiepitope Vaccine against Chicken Anemia Virus Disease.

Fatoba Abiodun Joseph AJ Adeleke Victoria T VT Maharaj Leah L Okpeku Moses M Adeniyi Adebayo A AA Adeleke Matthew A MA

Viruses 20220630 7

Chicken anemia virus (CAV) causes severe clinical and sub-clinical infection in poultry globally and thus leads to economic losses. The drawbacks of the commercially available vaccines against CAV disease signal the need for a novel, safe, and effective vaccine design. In this study, a multiepitope vaccine (MEV) consisting of T-cell and B-cell epitopes from CAV viral proteins (VP1 and VP2) was computationally constructed with the help of linkers and adjuvant. The 3D model of the MEV construct wa ...[more]

PMID: 35891436

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Project description:Since 1997, highly pathogenic avian influenza viruses, such as H5N1, have been recognized as a possible pandemic hazard to men and the poultry business. The rapid rate of mutation of H5N1 viruses makes the whole process of designing vaccines extremely challenging. Here, we used an in silico approach to design a multi-epitope vaccine against H5N1 influenza A virus using hemagglutinin (HA) and neuraminidase (NA) antigens. B-cell epitopes, Cytotoxic T lymphocyte (CTL) and Helper T lymphocyte (HTL) were predicted via IEDB, NetMHC-4 and NetMHCII-2.3 respectively. Two adjuvants consisting of Human β-defensin-3 (HβD-3) along with pan HLA DR-binding epitope (PADRE) have been chosen to induce more immune response. Linkers including KK, AAY, HEYGAEALERAG, GPGPGPG and double EAAAK were utilized to link epitopes and adjuvants. This construct encodes a protein having 350 amino acids and 38.46 kDa molecular weight. Antigenicity of ~ 1, the allergenicity of non-allergen, toxicity of negative and solubility of appropriate were confirmed through Vaxigen, AllerTOP, ToxDL and DeepSoluE, respectively. The 3D structure of H5N1 was refined and validated with a Z-Score of - 0.87 and an overall Ramachandran of 99.7%. Docking analysis showed H5N1 could interact with TLR7 (docking score of - 374.08 and by 4 hydrogen bonds) and TLR8 (docking score of - 414.39 and by 3 hydrogen bonds). Molecular dynamics simulations results showed RMSD and RMSF of 0.25 nm and 0.2 for H5N1-TLR7 as well as RMSD and RMSF of 0.45 nm and 0.4 for H5N1-TLR8 complexes, respectively. Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) confirmed stability and continuity of interaction between H5N1-TLR7 with the total binding energy of - 29.97 kJ/mol and H5N1-TLR8 with the total binding energy of - 23.9 kJ/mol. Investigating immune response simulation predicted evidence of the ability to stimulate T and B cells of the immunity system that shows the merits of this H5N1 vaccine proposed candidate for clinical trials.

Project description:Infectious bursal disease virus is the causative agent of infectious bursal disease (Gumboro disease), a highly contagious immunosuppressive disease of chicken with a substantial economic impact on small- and large-scale poultry industries worldwide. Currently, live attenuated vaccines are widely used to control the disease in chickens despite their issues with safety (immunosuppression and bursal atrophy) and efficiency (breaking through the maternally-derived antibody titer). To overcome the drawbacks, the current study has, for the first time, attempted to construct a computational model of a multiepitope based vaccine candidate against infectious bursal disease virus, which has the potential to overcome the safety and protection issues found in the existing live-attenuated vaccines. The current study used a reverse vaccinology based immunoinformatics approach to construct the vaccine candidate using major and minor capsid proteins of the virus, VP2 and VP3, respectively. The vaccine construct was composed of four CD8+ epitopes, seven CD4+ T-cell epitopes, 11 B-cell epitopes and a Cholera Toxin B adjuvant, connected using appropriate flexible peptide linkers. The vaccine construct was evaluated as antigenic with VaxiJen Score of 0.6781, immunogenic with IEDB score of 2.89887 and non-allergenic. The 55.64 kDa construct was further evaluated for its physicochemical characteristics, which revealed that it was stable with an instability index of 16.24, basic with theoretical pI of 9.24, thermostable with aliphatic index of 86.72 and hydrophilic with GRAVY score of -0.256. The docking and molecular dynamics simulation studies of the vaccine construct with Toll-like receptor-3 revealed fair structural interaction (binding affinity of -295.94 kcal/mol) and complex stability. Further, the predicted induction of antibodies and cytokines by the vaccine construct indicated the possible elicitation of the host's immune response against the virus. The work is a significant attempt to develop next-generation vaccines against the infectious bursal disease virus though further experimental studies are required to assess the efficacy and protectivity of the proposed vaccine candidate in vivo.

Dataset Information

Design of a Multiepitope Vaccine against Chicken Anemia Virus Disease.

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Design of a Multiepitope Vaccine against Chicken Anemia Virus Disease.

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