免疫信息学方法设计针对恶性疟原虫疟疾的多表位疫苗。

Immunoinformatics approach for multi-epitope vaccine design against P. falciparum malaria.

机构信息

Discipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Westville, South Africa.

Discipline of Chemical Engineering, University of KwaZulu-Natal, Howard Campus, Durban 4041, South Africa.

出版信息

Infect Genet Evol. 2021 Aug;92:104875. doi: 10.1016/j.meegid.2021.104875. Epub 2021 Apr 24.

Abstract

Plasmodium falciparum (P. falciparum) is a leading causative agent of malaria, an infectious disease that can be fatal. Unfortunately, control measures are becoming less effective over time. A vaccine is needed to effectively control malaria and lead towards the total elimination of the disease. There have been multiple attempts to develop a vaccine, but to date, none have been certified as appropriate for wide-scale use. In this study, an immunoinformatics method is presented to design a multi-epitope vaccine construct predicted to be effective against P. falciparum malaria. This was done through the prediction of 12 CD4+ T-cell, 10 CD8+ T-cell epitopes and, 1 B-cell epitope which were assessed for predicted high antigenicity, immunogenicity, and non-allergenicity through in silico methods. The Human Leukocyte Antigen (HLA) population coverage showed that the alleles associated with the epitopes accounted for 78.48% of the global population. The CD4+ and CD8+ T-cell epitopes were docked to HLA-DRB107:01 and HLA-A32:01 successfully. Therefore, the epitopes were deemed to be suitable as components of a multi-epitope vaccine construct. Adjuvant RS09 was added to the construct to generate a stronger immune response, as confirmed by an immune system simulation. Finally, the structural stability of the predicted multi-epitope vaccine was assessed using molecular dynamics simulations. The results show a promising vaccine design that should be further synthesised and assessed for its efficacy in an experimental laboratory setting.

摘要

疟原虫(P. falciparum)是疟疾的主要病原体,疟疾是一种可致命的传染病。不幸的是,随着时间的推移,控制措施的效果越来越差。需要一种疫苗来有效控制疟疾,以实现彻底消除该疾病。已经有多次尝试开发疫苗,但迄今为止,没有一种被证明适合广泛使用。在这项研究中,提出了一种免疫信息学方法来设计一种多表位疫苗构建体,预测对疟原虫疟疾有效。这是通过预测 12 个 CD4+ T 细胞、10 个 CD8+ T 细胞表位和 1 个 B 细胞表位来实现的,这些表位通过计算方法评估了预测的高抗原性、免疫原性和非变应原性。人类白细胞抗原(HLA)群体覆盖率表明,与表位相关的等位基因占全球人口的 78.48%。CD4+和 CD8+ T 细胞表位成功与 HLA-DRB107:01 和 HLA-A32:01 对接。因此,这些表位被认为适合作为多表位疫苗构建体的组成部分。佐剂 RS09 被添加到构建体中,以产生更强的免疫反应,这通过免疫系统模拟得到了证实。最后,使用分子动力学模拟评估了预测的多表位疫苗的结构稳定性。结果表明,这是一种有前途的疫苗设计,应该进一步合成,并在实验实验室环境中评估其疗效。

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