Daniel A. Adediran

Conference 2023 Presentation

Project title

mRNA VACCINE DESIGN FOR LASSA VIRUS INFECTION: EXPLORATION OF GLYCOPROTEIN AND NUCLEOPROTEIN

Authors and Affiliations

Daniel Adewole Adediran1, Seun Elijah Olufemi1, Tosin Titus Olaniran1, Micheal Oluwafemi Adeniyi1, Mercy Temiloluwa Ogunlowo1, Aanuoluwapo Olonade1, Anietie Femi Udoh1, Victoria Oluwapelumi Adekanola1, Glory Samuel Oluseyi1, Janet Abisola Omilola1, Olatunji M. Kolawole3, Julius Kola Oloke4, Elijah Kolawole Oladipo1,2

1. Genomics Unit, Helix Biogen Institute, Ogbomoso, Oyo State, Nigeria.
2. Department of Microbiology, Laboratory of Molecular Biology, Immunology and Bioinformatics, Adeleke University, Ede, Osun State Nigeria.
3. Department of Microbiology, University of Ilorin, Ilorin, Kwara State Nigeria.
4. Department of Natural Science, Precious Cornerstone, Ibadan, Oyo State, Nigeria.

Abstract

Background

Over 5,000 people die each year from the viral hemorrhagic disease referred to as Lassa fever (LASV) and is highly endemic in western Africa. Vaccines have long and continue been the most effective preventive tool against infectious diseases. Although there is currently no available vaccine to protect against the LASV infection, new advances in vaccine technology based on messenger RNA methods have been considered for a number of communicable illnesses, including SARS-CoV-2.

Methods

In this study, the authors construct mRNA against the Lassa virus using immunoinformatic approach. The EMBOSS server was used to translate the genome sequences retrieved from four Africa countries (Nigeria, Guinea, Liberia, and Sierra Leone) of the virus’s glycoprotein and nucleoprotein genes into their protein sequences. T cell epitopes and linear B-cell epitopes were predicted, validated, and tested for antigenicity, allergenicity, and toxicity. Eight epitopes (both T cells and B cells), flexible linkers, a highly immunogenic adjuvant, MHC I-targeting domain (MITD), and a signal peptide are the subunits that makes up the mRNA vaccine construct.

Results

The vaccine designed was predicted to have a molecular weight (MW) of 251.7 kDa, which is significantly higher than the threshold, slightly basic, and with an instability index of 49.63. Further investigation revealed that the mRNA vaccine candidate is hydrophilic, thermostable, non-toxic, and non-allergenic. The potential of the vaccine to induce the innate and adaptive immune response, was demonstrated by molecular docking of the TLR2, TLR3 and TLR9 which shows high binding affinity for all the TLRs on further validation via molecular dynamic simulation.

Conclusions

The designed mRNA vaccine has been demonstrated computationally to be a promising candidate for combating Lassa virus infection and therefore further research studies needs to be done via in vitro and in vivo techniques for validation of it efficiency and potency in elicitng immune response against Lassa virus.