Ziyou Zhou, Fei Zhu, Shiyang Ma, Caixia Tan, Hang Yang, Peipei Zhang, Yizhong Xu, Rongliu Qin, Yuying Luo, Jie Chen, Pinhua Pan
{"title":"Design of Cryptococcus neoformans multi-epitope vaccine based on immunoinformatics method.","authors":"Ziyou Zhou, Fei Zhu, Shiyang Ma, Caixia Tan, Hang Yang, Peipei Zhang, Yizhong Xu, Rongliu Qin, Yuying Luo, Jie Chen, Pinhua Pan","doi":"10.1093/mmy/myae080","DOIUrl":null,"url":null,"abstract":"<p><p>Cryptococcus neoformans is a widely distributed opportunistic pathogenic fungus. While C. neoformans commonly infects immunocompromised individuals, it can also affect those who are immunocompetent. Transmission of C. neoformans primarily occurs through the respiratory tract, leading to the development of meningitis. The mortality rate of Cryptococcal meningitis is high, and treatment options are limited. Cryptococcus neoformans infections pose a significant public health threat and currently lack targeted and effective response strategies. This study aimed to screen T lymphocyte (cytotoxic T lymphocyte and helper T lymphocyte) and B lymphocyte epitopes derived from four C. neoformans antigens and develop two multi-epitope vaccines by combining them with various adjuvants. Molecular docking results demonstrated that the vaccines bind stably to Toll-like receptor 4 ( and induce innate immunity. The credibility of the molecular docking results was validated through subsequent molecular dynamics simulations. Furthermore, the results of immune simulation analyses underscored the multi-epitope vaccine's capability to effectively induce robust humoral and cellular immune responses within the host organism. These two vaccines have demonstrated theoretical efficacy against C. neoformans infection as indicated by computer analysis. Nevertheless, additional experimental validation is essential to substantiate the protective efficacy of the vaccines.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical mycology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/mmy/myae080","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
Cryptococcus neoformans is a widely distributed opportunistic pathogenic fungus. While C. neoformans commonly infects immunocompromised individuals, it can also affect those who are immunocompetent. Transmission of C. neoformans primarily occurs through the respiratory tract, leading to the development of meningitis. The mortality rate of Cryptococcal meningitis is high, and treatment options are limited. Cryptococcus neoformans infections pose a significant public health threat and currently lack targeted and effective response strategies. This study aimed to screen T lymphocyte (cytotoxic T lymphocyte and helper T lymphocyte) and B lymphocyte epitopes derived from four C. neoformans antigens and develop two multi-epitope vaccines by combining them with various adjuvants. Molecular docking results demonstrated that the vaccines bind stably to Toll-like receptor 4 ( and induce innate immunity. The credibility of the molecular docking results was validated through subsequent molecular dynamics simulations. Furthermore, the results of immune simulation analyses underscored the multi-epitope vaccine's capability to effectively induce robust humoral and cellular immune responses within the host organism. These two vaccines have demonstrated theoretical efficacy against C. neoformans infection as indicated by computer analysis. Nevertheless, additional experimental validation is essential to substantiate the protective efficacy of the vaccines.
新生隐球菌是一种广泛分布的机会致病真菌。虽然新型隐球菌通常会感染免疫力低下的人,但它也会影响免疫力正常的人。新型隐球菌主要通过呼吸道传播,导致脑膜炎的发生。隐球菌脑膜炎的死亡率很高,而且治疗方法有限。新型隐球菌感染对公共卫生构成重大威胁,目前缺乏有针对性的有效应对策略。本研究旨在筛选从四种新型隐球菌抗原中提取的 T 淋巴细胞(CTL、HTL)和 B 淋巴细胞(LBL)表位,并将其与各种佐剂结合开发出两种多表位疫苗。分子对接结果表明,疫苗能与 TLR4 稳定结合并诱导先天性免疫。随后的分子动力学模拟验证了分子对接结果的可信度。此外,免疫模拟分析的结果还强调了多表位疫苗在宿主机体内有效诱导强大的体液和细胞免疫反应的能力。计算机分析表明,这两种疫苗对新型隐球菌感染具有理论疗效。不过,要证实疫苗的保护效力,还需要更多的实验验证。
期刊介绍:
Medical Mycology is a peer-reviewed international journal that focuses on original and innovative basic and applied studies, as well as learned reviews on all aspects of medical, veterinary and environmental mycology as related to disease. The objective is to present the highest quality scientific reports from throughout the world on divergent topics. These topics include the phylogeny of fungal pathogens, epidemiology and public health mycology themes, new approaches in the diagnosis and treatment of mycoses including clinical trials and guidelines, pharmacology and antifungal susceptibilities, changes in taxonomy, description of new or unusual fungi associated with human or animal disease, immunology of fungal infections, vaccinology for prevention of fungal infections, pathogenesis and virulence, and the molecular biology of pathogenic fungi in vitro and in vivo, including genomics, transcriptomics, metabolomics, and proteomics. Case reports are no longer accepted. In addition, studies of natural products showing inhibitory activity against pathogenic fungi are not accepted without chemical characterization and identification of the compounds responsible for the inhibitory activity.