Exploring Lassa Virus Proteome to Design a Multi-epitope Vaccine Through Immunoinformatics and Immune Simulation Analyses

Abstract

Lassa virus (LASV) is responsible for a type of acute viral haemorrhagic fever referred to as Lassa fever. Lack of adequate treatment and preventive measures against LASV resulted in a high mortality rate in its endemic regions. In this study, a multi-epitope vaccine was designed using immunoinformatics as a prophylactic agent against the virus. Following a rigorous assessment, the vaccine was built using T-cell (N CTL = 8 and N HTL = 6) and B-cell (N LBL = 4) epitopes from each LASV-derived protein in addition with suitable linkers and adjuvant. The physicochemistry, immunogenic potency and safeness of the designed vaccine (~ 68 kDa) were assessed. In addition, chosen CTL and HTL epitopes of our vaccine showed 97.37% worldwide population coverage. Besides, disulphide engineering also improved the stability of the chimeric vaccine. Molecular docking of our vaccine protein with toll-like receptor 2 (TLR2) showed binding efficiency followed by dynamics simulation for stable interaction. Furthermore, higher levels of cell-mediated immunity and rapid antigen clearance were suggested by immune simulation and repeated-exposure simulation, respectively. Finally, the optimized codons were used in in silico cloning to ensure higher expression within E. coli K12 bacterium. With further assessment both in vitro and in vivo, we believe that our proposed peptide-vaccine would be potential immunogen against Lassa fever.

Discovery of potential immune epitopes and peptide vaccine design - a prophylactic strategy against Rift Valley fever virus

“…With the emergence of new computational technology and widely available databases, different strategies are now available for designing and developing epitope-based vaccines following immunoinformatics expedients 73,74 . Vaccines against multitudes of viruses such as SARS-CoV-2, Ebola, Lassa, hepatitis C, Oropouche, Dengue and many more in the pipeline are prime examples of a structural vaccinology approach applied to the design of a multiepitope vaccine model 17,19,[75][76][77][78][79] . In this study, our primary focus was to devise a multiepitope vaccine with the ability to produce robust immunity against RVFV having considered all the parameters of a subunit vaccine.…”

“…Thus, the viral glycoproteins were targeted for our multiepitope vaccine design, which would be constructed using glycoprotein epitope sequences evoking an immune response inside the human system 13,14 . At present, epitope-based candidate vaccine design against viruses and bacteria as well as parasites has become very popular and has been done previously [15][16][17][18][19][20] . Multiepitope vaccines consist of short peptide fragments of immunogenic stimulants, which trigger a strong immune response and allow for a significantly lower chance of allergenic reactions inside the host system 21 .…”

Designing a conserved peptide-based subunit vaccine against SARS-CoV-2 using immunoinformatics approach

“…The deformability is dependent on the potential of a specific molecule to deform at its residues. The eigenvalue represents how rigid the motion is, and it has a relationship with the energy required to deform the structure of the vaccine-receptor complex as low eigenvalue depicts structures that can be easily deformed (López-Blanco et al 2014 ; Sayed et al 2020 ).…”

In silicoapproach for designing of a multi-epitope based vaccine against novel Coronavirus (SARS-COV-2)

“…Finally, the binding affinity between the TLR3 receptor and vaccine construct was calculated by using ClusPro 2.0 server (Kozakov et al ., 2017). The server uses three consecutive steps like rigid body docking, clustering of lowest energy structure, and structural refinement by energy minimization (Sayed et al ., 2020). The best docked complex was obtained based on the lowest energy weighted score and docking efficiency.…”