Immunoinformatics Approach for the Identification of T-Cell Epitopes from 6-Cysteine P48/45 Protein of Plasmodium falciparum for Malaria Vaccine Development Jofrishal (a), Rizarullah (b*), Rahmatul Fajri (c), Tirta Setiawan (d)
a) Chemistry Department, Faculty of Teacher Training and Education, Universitas Samudra, Langsa, 24415, Indonesia
b) Department of Biochemistry, Faculty of Medicine, Abulyatama University, Jl. Blangbintang Lama, Aceh Besar 23372, Indonesia
*rizarullah_fk[at]abulyatama.ac.id
c) Chemistry Department, Faculty of Science and Technology, Universitas Samudra, Langsa, 24415, Indonesia
d) Program Study of Data Science, Faculty of Science, Institut Teknologi Sumatera, South of Lampung, Indonesia
Abstract
Malaria caused by Plasmodium falciparum is one of the deadly parasitic diseases that requires new strategies in vaccine development. In this study, we used an immunoinformatic approach to explore the target protein 6-Cysteine P48/45 of Plasmodium falciparum strain 3D7, which is known to have an important role in the infection process and parasite life cycle. This protein was chosen for its ability to trigger a strong immune response, making it a potential candidate for malaria vaccine development. This study aims to identify and predict cytotoxic T cell (CTL) and helper T cell (HTL) epitopes derived from the 6-Cysteine P48/45 protein as potential vaccine candidates through an immunoinformatic approach. Immunoinformatic studies were conducted using several bioinformatics software to predict CTL and HTL epitopes of 6-Cysteine P48/45 protein. Epitope prediction was based on affinity to MHC class I and class II molecules. The resulting epitopes were further evaluated based on immunogenicity, allergenicity and conservation across strains. The assessment is done to ensure the candidate epitopes generated have potential as effective vaccine targets. Potential epitopes were linked with AAY and GPGPG linkers. The multi-epitope vaccine protein sequences obtained were predicted for their terse structures using alphafold 3. This study successfully identified five cytotoxic T cell (CTL) and five helper T cell (HTL) epitopes that have high affinity to MHC class I and MHC class II molecules. The results of interaction analysis with Toll Like Receptor 4 (TLR4) obtained a binding free energy value of 109.26 kcal/mol. Immune response simulation results show that the multiepitope vaccine candidate can activate the adaptive and humoral immune systems and generate long-term B cell memory. Based on these results, the development of this multi-epitope malaria vaccine is a significant step forward in the effort to create a potential malaria vaccine.
