Structural and Immunogenicity Analysis of Reconstructed Ancestral and Consensus P48/45 for cross-species Antimalaria Vaccine

The development of the antimalaria vaccine holds a promising future in malaria control. One of the antimalaria vaccine strategies known as the transmission-blocking vaccine is designed to inhibit the parasite transmission between human and mosquito by targeting parasite gametocyte. Previously, we found that P48/45 that include in the 6-Cysteine protein family shared by Plasmodium sp. We also detected vaccine properties that possess by all human-infecting Plasmodium and could be used as a cross-species antimalaria vaccine. In this study, we investigated the efficacy of P48/45 through the ancestral and consensus reconstruction approach. P48/45 phylogenetic and time tree analysis was done by RAXML and BEAST2. GRASP server and Ugene software were used to reconstructed ancestral and consensus sequences, respectively. The protein structural prediction was done by using inspired and Rosetta program. Each protein characteristic of P48/45 was analyzed by assessing hydrophobicity and Post-Translational Modification sites. Meanwhile, the Epitope sequence for B-cell, T-cell, and MHC was determined using an immunoinformatic approach. Lastly, molecular docking simulation was done to determine native binding interactions of P48/45-P230. The result showed a distinct protein characteristic of ancestral and consensus sequences. The immunogenicity analysis revealed the number of epitopes in the ancestral sequence is greater. The study also found a conserved epitope located in the binding site and consists of specific Post-Translational Modification sites. Hence, our research provides detailed insight into ancestral and consensus P48/45 efficacy