Designing of a multiepitope-based chimeric vaccine against dengue virus serotype 3 (DENV-3) through next generation reverse vaccinology approaches

Abstract

The dengue virus (DENV) causes dengue infection and has become a significant global public health concern. The successful application of immunotherapies in treating dengue infection has paved the way for developing various treatment strategies. Among these strategies, the multiepitope vaccine has emerged as a promising approach. We applied an in silico immune-informatics approach to develop a multiepitope vaccine including MHC-I, MHC-II, and B cell epitopes of the NS1, E, and M proteins. The vaccine was found to be a structurally stable protein (Z score = −4.71), indicating its effectiveness. High affinity was shown by molecular docking studies between the vaccine and human receptors (toll-like receptor 2 and toll-like receptor 4). Following codon optimization and in silico cloning, the vaccine was successfully expressed (CAI value of 0.9588) after being inserted into the pET-30a (+) plasmid of the E. coli K12 strain. However, the vaccine's potential to elicit immunological responses (such as B cell, T cell, antibody, and cytokine responses) against the dengue virus serotype 3 (DENV-3) has been established through immune simulation. The majority of existing dengue vaccines have shown little efficacy in the management of dengue infection. Furthermore, there is currently no licenced multiepitope vaccine for dengue virus serotype 3 (DENV-3) that encompasses all three significant proteins. Consequently, our proposed vaccine has the potential to be an effective weapon in combating dengue infection. Further studies should be conducted to evaluate the safety, effectiveness, and potential adverse effects of this multiepitope vaccine in human subjects to facilitate its further development.

Keywords

• DENV-3
• Multiepitope vaccine
• Molecular docking
• Immunotherapy
• Bangladesh