Uddin Md Bashir, Tanni Fatema Yeasmin, Hoque Syeda Farjana, Sajib Emran Hossain, Faysal Md Atik, Rahman Md Anisur, Galib Asaduzzaman, Emon Ahsan Al, Hossain Md Mukter, Hasan Mahmudul, Ahmed Syed Sayeem Uddin
Department of Medicine, Sylhet Agricultural University, Sylhet, Bangladesh.
Department of Microbiology & Immunology, University of Texas Medical Branch (UTMB), Galveston, United States.
Transbound Emerg Dis. 2022 Nov;69(6):3548-3561. doi: 10.1111/tbed.14718. Epub 2022 Nov 7.
Lumpy skin disease (LSD) is a fulminant infectious disease that mostly affects cattle and causes considerable economic loss throughout the globe. This study was conducted to develop a new multi-epitope-based vaccine against LSD that can elicit immunological responses using an in silico reverse vaccinology approach. Initially, three antigenic proteins, protein E5, E3 ubiquitin-protein ligase LAP and 62 kDa protein, were manipulated to recognize potential T-cell and B-cell epitopes. To identify superior epitopes, a variety of bioinformatic techniques including antigenicity testing, transmembrane topology screening, allergenicity assessment, conservancy analysis, and toxicity evaluation were used. Finally, three new subunit vaccines (construct V1, V2 and V3) were developed employing the most effective epitopes, suitable adjuvants, pan HLA DR-binding epitope (PADRE) and linkers. Then, based on the antigenicity, solubility, and validation score of the 3D structures, construct V2 was chosen as one of the best candidate vaccines. The results of the molecular dynamic simulation and disulphide engineering indicated that the vaccine (construct V2) was stable. Additionally, the immunological simulation findings supported the vaccine candidate's ability to trigger humoral and cellular immune responses. Further validation of the proposed vaccine candidate may necessitate additional in vitro and in vivo investigations.
结节性皮肤病（LSD）是一种急性传染病，主要影响牛群，并在全球范围内造成相当大的经济损失。本研究旨在利用计算机反向疫苗学方法开发一种新型的基于多表位的抗LSD疫苗，该疫苗能够引发免疫反应。最初，对三种抗原蛋白，即E5蛋白、E3泛素蛋白连接酶LAP和62 kDa蛋白进行处理，以识别潜在的T细胞和B细胞表位。为了鉴定出优势表位，使用了多种生物信息学技术，包括抗原性测试、跨膜拓扑结构筛选、致敏性评估、保守性分析和毒性评估。最后，利用最有效的表位、合适的佐剂、泛HLA DR结合表位（PADRE）和连接子，开发了三种新型亚单位疫苗（构建体V1、V2和V3）。然后，根据三维结构的抗原性、溶解性和验证分数，选择构建体V2作为最佳候选疫苗之一。分子动力学模拟和二硫键工程的结果表明，该疫苗（构建体V2）是稳定的。此外，免疫模拟结果支持候选疫苗引发体液免疫和细胞免疫反应的能力。对所提出的候选疫苗进行进一步验证可能需要额外的体外和体内研究。
