Rational design of B-cell and T-cell multi epitope-based vaccine against Zika virus, an in silico study

Abstract

The Zika virus (ZKV) is a single-stranded positive-sense, enveloped RNA virus. Zika infection during pregnancy can cause congenital microcephaly, Guillain-Barré syndrome, miscarriage, and other CNS abnormalities. The world needs safe and effective vaccinations to fight against ZIKV infection since vaccination is generally regarded as one of the most effective ways to prevent infectious diseases. In the present work, we used immunoinformatics and docking studies to construct a vaccine containing multi-epitopes using the structural and non-structural proteins of ZKV. The structural models of ZKV proteins (PrE, PrM, NS1, and NS2A) were constructed using Pyre2 and RaptorX servers. The epitopes of B-cell, T-cell (HTL and CTL), and IFN-γ were predicted, and each epitope’s immunogenic nature and physiochemical properties were confirmed. As an adjuvant, the CPG-Oligodeoxynucleotide, an agonist of Toll-like receptor 9 (TLR9), is associated to cytotoxic T-lymphocytes (CTL) epitopes via PAPAP linker. To assess the binding affinity and the tendency of the designed vaccine to induce an immune response through TLR9, molecular docking was done. In the next step, molecular dynamics (MD) simulation to 100 nanoseconds (ns) was used to evaluate the stability of the interaction of the designed vaccine with TLR9. The designed vaccine is predicted to be highly antigenic, non-toxic, soluble, and stable with low flexibility in MD simulation. MD studies indicated that the finalized vaccine-TLR9 docked complex was stable during simulation time. The vaccine construct is able to stimulate both humoral and cellular immune responses. We suppose that our constructed model of the vaccine may have the ability to induce the host immune response against ZKV. Further studies, including in vitro and in vivo experimental analyses, are needed to prove the constructed vaccine’s efficacy with multi-epitopes.

Communicated by Ramaswamy H. Sarma

Keywords:

• Multi-epitope
• adjuvant
• subunit vaccine
• vaccine
• Zika virus (ZKV)
• molecular docking
• immunoinformatics

Author contributions

MG, SB, and KA: study conception and design, writing original draft, methodology and software. SM and AS: review and editing. AG: supervision.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sector.