Computational vaccinology approach: Designing an efficient multi-epitope peptide vaccine againstCryptococcus neoformans var. grubii’sheat shock 70KDa protein

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 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).

Comparison of HIV-1 Vif and Vpu accessory proteins for delivery of polyepitope constructs harboring Nef, Gp160 and P24 using various cell penetrating peptides

“…In order to design multiepitope peptide constructs using immunoinformatic analysis, at first, we determined potentially immune-protective epitopes. T cells identify antigens as short peptide segment in association with major histocompatibility complex (MHC) molecules on antigen-presenting cells [6]. There are two categories of T-cells: a) CD8 + T cytotoxic cells which recognize peptides displayed by MHC-I molecules, b) CD4 + T helper cells which recognize epitopes related to MHC-II molecules.…”

“…MHC-II binding prediction was not as advanced as MHC-I binding prediction, i . e ., it is still developing at a fast rate [6].…”

“…To ensure the universal coverage within a heterogeneous population, it is crucial to calculate global population coverage for the chosen epitopes since the HLAs are among the most polymorphic proteins and vary among different geographical regions around the world [6]. The epitopes have a different binding profile with various HLA alleles; thus, population coverage must be taken into a different set of alleles to cover all regions and to get desirable immune response in all individuals within a given population.…”

“…The epitopes have a different binding profile with various HLA alleles; thus, population coverage must be taken into a different set of alleles to cover all regions and to get desirable immune response in all individuals within a given population. For that reason, all promising MHC-I and MHC-II epitope candidates were assessed for population coverage against different geographic areas through IEDB population coverage calculation tool at http://tools.iedb.org/population/ [6].…”

“…Compared to traditional vaccines, subunit vaccines showed several benefits including cost-effectiveness, great safety profile, high stability, low toxicity, and ease of manufacturing process. For example, peptide vaccination could be considered as an efficient strategy not only in viral infections, but also in Alzheimer’s disease and even allergic reactions [4, 6]. However, the determination of epitopes or antigens that can enhance efficient preventive or therapeutic immune responses is one of the most important steps in subunit vaccine development [7].…”