In silico Designing of a Multi-epitope-based Subunit Vaccine against
SARS-CoV-2 (Delta Variant) by Exploiting Its Structural Proteins: A
Reverse Vaccinomics and Immunoinformatics Approach
Authors: Halder Sajal Kumar , Sharma Ashish Ranjan , Al Arian Tawsif , Saha Samantha , Shil Aparna , Rafi Md. Oliullah , Sarker Satya Ranjan , Alam Md. Nuhu , Himel Mahbubul Kabir , Hasan Md. Ashraful , Shawan Mohammad Mahfuz Ali Khan 
Published: January 2024

Background:
The continuously emerging novel strains of SARS-CoV-2 remain a menace
to the global population. The vicious delta variant (originated in India) is considered one of the most
infectious/contagious variants of SARS-CoV-2. The transmission frequency of this variant is 225%
higher than other variants, extending its prevalence and causing a massive surge in the COVID-19
pandemic. It is also the most ravenous variant among others.

Objective:
Though the delta variant has already disappeared, it could re-emerge/come out at any time
with a more powerful strike than earlier. Therefore, to tackle such ferocity, this research is undertaken
with a next-generation vaccine development strategy to design a multi-epitope-based subunit vaccine
against the delta variant of SARS-CoV-2, which might boost the body's immunity.

Materials and Methods:
In the present investigation, reverse vaccinomics and immunoinformatics
approaches were adopted to create an immune-stimulating prospective vaccine candidate having B
cell, helper T cell (Th)/helper T lymphocyte (HTL), cytotoxic T cell (Tc)/cytotoxic T lymphocyte
(CTL), and interferon-gamma (IFN-γ) inducing epitopes by exploiting the SARS-CoV-2 (delta variant)
(GenBank: MZ724536.1) structural proteins: envelope glycoprotein (E), nucleocapsid phosphoprotein
(N), surface glycoprotein (S), and membrane glycoprotein (M). The established vaccine construct
was then completed by combining antigenic epitopes with adjuvants and linkers. Subsequently,
the 3D model of the suggested vaccine was created and docked with an immune receptor (Toll-Like
Receptor-4). A molecular dynamics (MD) simulation study was performed to confirm the binding
stability between the vaccine conjugate and TLR4. Later, an immune simulation study was carried
out to predict the in silico immune response of the vaccine candidate. To effectively express the developed
vaccine in a bacterial system (E. coli), in silico codon optimization and cloning were done in
an expression vector to manufacture it on a large scale.

Results:
According to the computational analysis, the vaccine candidate was found to be highly antigenic
while maintaining favorable properties for the human body. Molecular docking and dynamics
simulation study between the suggested vaccine construct and TLR4 immune receptor depicted it as
extremely efficient and stable, ensuring a proper immunological response within the host cell. Eventually,
an in silico immune simulation study of the vaccine candidate demonstrated a robust immune
response to vaccine administration.

Conclusion:
We have hypothesized that the constructed vaccine model is benign, stable, and immunogenic,
making it a promising/potent candidate for immune system stimulation against SARSCOV-
2 (DV). Hereof, wet lab-based investigations are needed to justify the competence of the novel
vaccine candidate towards the delta variant along with other variants of SARS-CoV-2.