Abstract:
Cryptococcus neoformans is the highest-ranked fungal pathogen in the Fungal Priority Pathogens List (FPPL) released by the World Health Organization (WHO). In this study, through in silico simulations, a multi-epitope vaccine against Cryptococcus neoformans was developed using the mannoprotein antigen (MP88) as a vaccine candidate. Following the retrieval of the MP88 protein sequences, these were used to predict antigenic B-cell and T-cell epitopes via the bepipred tool and the artificial neural network, respectively. Conserved B-cell epitopes AYSTPA, AYSTPAS, PASSNCK, and DSAYPP were identified as the most promising B-cell epitopes. While YMAADQFCL, VSYEEWMNY, and FQQRYTGTF were identified as the best candidates for CD8+ T-cell epitopes; and YARLLSLNA, ISYGTAMAV, and INQTSYARL were identified as the most promising CD4+ T-cell epitopes. The vaccine construct was modeled along with adjuvant and peptide linkers and the expasy protparam tool was used to predict the physiochemical properties. According to this, the construct vaccine was predicted to be antigenic, nontoxic, nonallergenic, soluble, stable, hydrophilic, and thermostable. Furthermore, the three-dimensional structure was also used in docking analyses with Toll-like receptor (TLR4). Finally, the cDNA of vaccine was successfully cloned into the E. coli pET-28a (+) expression vector. The results presented here could contribute towards the design of an effective vaccine against Cryptococcus neoformans.
摘要:
新生隐球菌是世界卫生组织(WHO)发布的真菌优先病原体清单(FPPL)中排名最高的真菌病原体。在这项研究中,通过计算机模拟,利用甘露糖蛋白抗原(MP88)作为候选疫苗,开发了一种针对新生隐球菌的多表位疫苗.在检索MP88蛋白序列后,这些被用来预测抗原性B细胞和T细胞表位通过bepipred工具和人工神经网络,分别。保守的B细胞表位AYSTPA,AYSTPAS,PASSNCK,和DSAYPP被鉴定为最有前途的B细胞表位。而YMAADQFCL,VSYEEWMNY,和FQQRYTGTF被鉴定为CD8+T细胞表位的最佳候选;和YARLLSLNA,ISYGTAMAV,和INQTSYARL被鉴定为最有前途的CD4+T细胞表位。将疫苗构建体与佐剂和肽接头一起建模,并使用expasyprotparam工具来预测理化性质。据此,预测构建疫苗是抗原性的,无毒,非过敏性,可溶性,稳定,亲水性,和热稳定。此外,三维结构也用于与Toll样受体(TLR4)的对接分析.最后,将疫苗的cDNA成功克隆到大肠杆菌pET-28a(+)表达载体中。本文提出的结果可能有助于设计针对新生隐球菌的有效疫苗。