Computational Design of a Multi-epitope Vaccine Against Clostridium chauvoei: An Immunoinformatics Approach

Onchocerciasis is a skin and eye disease that exerts a heavy socio-economic burden, particularly in sub-Saharan Africa, a region which harbours greater than 96% of either infected or at-risk populations. The elimination plan for the disease is currently challenged by many factors including amongst others; the potential emergence of resistance to the main chemotherapeutic agent, ivermectin (IVM). Novel tools, including preventative and therapeutic vaccines, could provide additional impetus to the disease elimination tool portfolio. Several observations in both humans and animals have provided evidence for the development of both natural and artificial acquired immunity. In this study, immuno-informatics tools were applied to design a filarial-conserved multi-epitope subunit vaccine candidate, (designated Ov-DKR-2) consisting of B-and T-lymphocyte epitopes of eight immunogenic antigens previously assessed in pre-clinical studies. The high-percentage conservation of the selected proteins and epitopes predicted in related nematode parasitic species hints that the generated chimera may be instrumental for cross-protection. Bioinformatics analyses were employed for the prediction, refinement, and validation of the 3D structure of the Ov-DKR-2 chimera. In-silico immune simulation projected significantly high levels of IgG1, T-helper, T-cytotoxic cells, INF-γ, and IL-2 responses. Preliminary immunological analyses revealed that the multi-epitope vaccine candidate reacted with antibodies in sera from both onchocerciasis-infected individuals, endemic normals as well as loiasis-infected persons but not with the control sera from European individuals. These results support the premise for further characterisation of the engineered protein as a vaccine candidate for onchocerciasis.

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Computational Design of a Novel Candidate Multi-Epitope Vaccine to Boost Immune Responses against SARS‐COV‐2

Letters in Drug Design & Discovery ◽

10.2174/1570180818666211011094822 ◽

2021 ◽

Vol 18 ◽

Author(s):

Shiva Mohammadi ◽

Soudabe Kavusi Pour ◽

Mahdi Barazesh ◽

Yadollah Bahrami ◽

Sajad Jalili

Keyword(s):

T Lymphocyte ◽

Animal Studies ◽

Cytotoxic T Lymphocyte ◽

Cost Effective ◽

Computational Design ◽

Candidate Vaccine ◽

Effective Vaccine ◽

Epitope Vaccine ◽

Time Saving ◽

Binding Interface

Background: The fast development of an effective vaccine is the major demand for protection against the SARS-COV-2 virus outbreak. Immuno-informatics tools are time-saving and cost-effective methods to hasten the design and establishment of a proficient multi-peptide candidate vaccine. The utilization of multi-epitope-based vaccines has demonstrated to be a promising immunization approach against viruses due to the induction of long-term protective immunity. Method: In the present study, a complete computational approach was conducted to design a multi-epitope-based vaccine composed of cytotoxic T lymphocyte and helper T lymphocyte epitopes of Spike and Nucleocapsid proteins conserved regions. The potential viral peptides as the candidate vaccine were screened regarding convenient features like hydrophilicity, flexibility, antigenicity, and charged properties. In the next step, the vaccine efficacy needed to be improved by an immune adjuvant. For this purpose, the C-terminal domain of heat shock protein gp96 (CT-GP96) was applied as a potent adjuvant for enhancing immunity. The final assembled construct was fused with the assistance of suitable linkers and cloned in a pET28a expression vector for overproduction of the vaccine in a bacterial host. Result: Following validation of the final construct in terms of its efficacy, stability, and exposure ability, molecular docking analysis was carried out to reveal its interaction with toll-like receptor 4, which is required to trigger the immune response. The molecular simulations by iMODS software confirmed the stability of the binding interface. Additionally, the computational cloning of the assembled vaccine in pET28a plasmid showed the possibility of producing a vaccine construct post-transformation in an E. coli host. Conclusion: The computational analysis indicated that this construct could be a potent prophylactic and therapeutic multi-epitope vaccine candidate against SARS‐COV‐2 once its effectiveness is verified by experimental and animal studies.

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