DESAIN VAKSIN MULTI-EPITOP SARS-COV-2 DENGAN PLATFORM MRNA MENGGUNAKAN PROTEIN NSP7, NSP8, NSP12, DAN S MELALUI PENDEKATAN REVERSE VACCINOLOGY

• Main Author: Nurrahma Azizah, Kamilia
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/66010
• Institution: Institut Teknologi Bandung

SARS-CoV-2 is a novel coronavirus that causes the COVID-19 disease, which in mid-April 2020 had reached 213 countries and had already infected about two million people since the first case on December 12, 2019 in Wuhan, China. Therefore, a vaccine that is safe, effective, and easily accessible to the public is crucial. A study was conducted to design a multiepitope vaccine with a non-replicating mRNA platform through a reverse vaccinology approach. The study began with the prediction and selection of B and T cell epitopes from the consensus sequences of spike protein (S), non-structural protein 7 (NSP7), non-structural protein 8 (NSP8), and non-structural protein 12 (NSP12) of SARS-CoV-2 originating from Africa, Asia, Europe, North America, and South America. The spike protein was chosen because it is an immunodominant antigen in CoV infection and contains neutralizing epitopes. The proteins NSP7, NSP8, and NSP12 were chosen because these three proteins have many activities and play a role in viral RNA synthesis, so they are expected to disrupt the activity of making RNA copies. Consensus sequences were mapped against B cell receptors and Human Leukocyte Antigen (HLA) class I and II alleles that were representative of the world population to predict B and T cell epitopes. Epitope candidates were selected by taking into account various predefined parameters. Seventeen T cell epitopes and one B cell epitope were produced which were predicted to have high antigenicity, non-allergenenic, non-toxic, >94% conservability, and hydrophilic. The vaccine construct was constructed using the 18 predicted epitopes, linked with GPGPG, (EAAAK)2, and AAY linkers, as well as an adjuvant in the form of a synthetic TLR-4 agonist RS-09. The resulting vaccine construct has a world population coverage of 99.81% and 47% of its amino acids are exposed for solvent accessibility. The results of the docking analysis showed that the construct complexed with TLR-2 and TLR-4 receptors showed negative Gibbs free energy, indicating good binding affinity. Further molecular dynamics, plasmid construct, in vivo and in vitro studies need to be carried out to validate the vaccine construct.