Introduction: Cryptococcosis is a ubiquitous opportunistic fungal disease caused by Cryptococcus neoformans var. grubii. It has high global morbidity and mortality among HIV patients and none-HIV carriers with 99% and 95% respectively. Furthermore, the increasing prevalence of undesired toxicity profile of antifungal, multi-drug resistant organism, and the scarcity of FDA authorized vaccines, where the hallmark in the present days. This study was undertaken to design a reliable multi-epitope peptide vaccine against highly conserved immunodominant heat shock 70KDa protein of Cryptococcus neoformans var. grubii that covers a considerable digit of the world population through implementing computational vaccinology approach. Materials and Methods: A total of 38 Sequences of Cryptococcus neoformans var. grubii's heat shock 70KDa protein were retrieved from NCBI protein database. Different prediction tools were used to analyze the aforementioned protein at Immune Epitope Database (IEDB) to discriminate the most promising Tcell and B-cell epitopes. Then the proposed epitopes were subjected to Population coverage analysis tool to compute global population's coverage. Finally, the projected epitopes were ranked based on their scores and binding modes through using Moe 2007 program. Outstanding Results and Conclusion: Our prime vaccine candidate was a putative ten promising epitopes (ANYVQASEK, NYVQASEK, KSVEKPAS, TPQQPPAQ, YVYDTRGKL, FYRQGAFEL, FTQLVAAYL, FFGGKVLNF, FDYALVQHF, and FINAQLVDV). Together, these epitopes are forecasted to trigger T lymphocytes, B lymphocytes, and immunological memory with overall population coverage above 90%. Accordingly, our in silico vaccine is expected to be the future multi-epitope peptide vaccine against Cryptococcus neoformans var. grubii's heat shock 70KDa protein that covers a significant figure of the entire world citizens. Therefore, there is a definite need for experimental validation for the carefully chosen vaccine candidates in vitro and in vivo to fortify their antigenic and immunogenic potentials. Additionally, further computational studies are needed to be conducted in pathogens-derived Heat shock 70KDa protein family, as it believed to find universal epitopes that might be overlapped with other pathogens-derived Hsp70.Keywords: Multi-epitope peptide vaccine, Computational vaccinology, Cryptococcus neoformans var. grubii, Cryptococcosis, in silico vaccine, Heat shock 70KDa protein (Hsp70).
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