Structure-based evaluation of the envelope domain III–nonstructural protein 1 (EDIII-NS1) fusion as a dengue virus vaccine candidate

Abstract

The lack of effective medicines or vaccines, combined with climate change and other environmental factors, annually subjects a significant proportion of the world’s inhabitants to the risk of dengue virus (DENV) infection. These conditions increase the likelihood of exposure to mosquito-borne diseases such as dengue fever. Hence, many research approaches tend to develop efficient vaccine candidates against the dengue virus. Therefore, we used immunoinformatics and bioinformatics to design a construction for developing a candidate vaccine against dengue virus serotypes. In this study, the in silico structure, containing the non-structural protein 1 region (NS1) (consensus and epitope), the envelope domain III protein (EDIII) as the structural part of the virus construction, and the bc-loop of envelope domain II (EDII) as the neutralizing and protected epitope, were employed. We utilized in silico tools to enhance the immunogenicity and effectiveness of dengue virus vaccine candidates. Evaluations included refining and validating physicochemical characteristics, B and T-cell epitopes, homology modeling, and the three-dimensional structure to assess the designed vaccine’s quality. In silico results for tertiary structure prediction and validation revealed high-quality modeling for all vaccine constructs. Additionally, the instructed model demonstrated stability throughout molecular dynamics simulation. The results of the immune simulation suggested that the titers of IgG and IgM could be raised to desirable values following injection into in vivo models. It can be concluded that the designed construct effectively induce humoral and cellular immunity and can be proposed as effective vaccine candidate against four dengue serotypes.

Communicated by Ramaswamy H. Sarma

Keywords:

• Dengue virus
• dengue vaccine
• molecular docking
• immunoinformatics
• epitope
• envelope domain (consensus)

Acknowledgement

The authors express their gratitude to the dedicated personnel in the Departments of Molecular Virology and Molecular Medicine at the Pasteur Institute of Iran, Tehran.

Authors’ contributions

ShM and RE: Investigation, Conceptualization, Formal Analysis, Writing - Original Draft, Data Curation. Mostafa SM: Supervision, Review, Editing conceptualization. AK: Supervision, Review, Editing, Conceptualization, Funding acquisition, Project Administration. All authors read, and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The research, conducted as part of the Ph.D. program with the project code TP-9356, was financially supported by the Pasteur Institute of Iran.