Abstract
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 non-HIV carriers with 99% and 95%, respectively. Furthermore, the increasing prevalence of undesired toxicity profile of antifungal, multidrug-resistant organisms and the scarcity of FDA-authorized vaccines were the hallmark in the present days. This study was undertaken to design a reliable epitope-based peptide vaccine through targeting highly conserved immunodominant heat shock 70 kDa protein of Cryptococcus neoformans var. grubii that covers a considerable digit of the world population through implementing a computational vaccinology approach. Materials and Methods A total of 38 sequences of Cryptococcus neoformans var. grubii's heat shock 70 kDa protein were retrieved from the NCBI protein database. Different prediction tools were used to analyze the aforementioned protein at the Immune Epitope Database (IEDB) to discriminate the most promising T-cell and B-cell epitopes. The proposed T-cell epitopes were subjected to the population coverage analysis tool to compute the global population's coverage. Finally, the T-cell projected epitopes were ranked based on their binding scores and modes using AutoDock Vina software. Results and Discussion. The epitopes (ANYVQASEK, QSEKPKNVNPVI, SEKPKNVNPVI, and EKPKNVNPVI) had shown very strong binding affinity and immunogenic properties to B-cell. (FTQLVAAYL, YVYDTRGKL) and (FFGGKVLNF, FINAQLVDV, and FDYALVQHF) exhibited a very strong binding affinity to MHC-I and MHC-II, respectively, with high population coverage for each, while FYRQGAFEL has shown promising results in terms of its binding profile to MHC-II and MHC-I alleles and good strength of binding when docked with HLA-C∗12:03. In addition, there is massive global population coverage in the three coverage modes. Accordingly, our in silico vaccine is expected to be the future epitope-based peptide vaccine against Cryptococcus neoformans var. grubii that covers a significant figure of the entire world citizens.
Highlights
Cryptococcosis is a ubiquitous opportunistic fungal disease caused by Cryptococcus neoformans var. grubii
A total of 38 heat shock 70 kDa protein of Cryptococcus neoformans var. grubii sequences with a length of 773 mer were retrieved in FASTA format from the National Centre for Biotechnology Information (NCBI) protein database (Accession No XP_ 012053205.1) on 30th July 2018 at https://www.ncbi.nlm .nih.gov/protein (Supplementary Table 5)
The overall analysis revealed seventeen promiscuous B-cell and T-cell epitopes that consist of four immunogenic continuous B-cell epitopes (ANYVQASEK, QSEKPKNVNPVI, SEKPKNVNPVI, and EKPKNVNPVI), seven discontinuous B-cell epitopes, and six immunogenic MHC-I and MHC-II epitopes (YVYDTRGKL, FYRQGAFEL, FTQLVAAYL, FFGGKVLNF, FINAQLVDV, and FDYALVQHF) that are proposed to be used in epitope-based vaccine designing
Summary
Cryptococcosis is a ubiquitous opportunistic fungal disease caused by Cryptococcus neoformans var. grubii. This study was undertaken to design a reliable epitope-based peptide vaccine through targeting highly conserved immunodominant heat shock 70 kDa protein of Cryptococcus neoformans var. This does not contradict the importance of B-cell response, which is considered a vital mechanism for inducing protection against cryptococcosis in individuals with impaired cell-mediated immunity [13,14,15] When it comes to immunomodulatory factors, it is given that C. neoformans expresses a significant number of immuneproteomic factors that evoke host immunity that could be useful targets as diagnostic markers or vaccines [16,17,18,19,20]. Throughout evolution, the Hsp family is a highly conserved cell-surface protein and widely expressed in Plasmodium [24], Trypanosoma, Schistosoma, Leishmania [25], Toxoplasma [26], Candida [27, 28], Histoplasma [29, 30], and Mycobacterium [31] species
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