Integrative Biochemistry & Immunology Laboratory, Department of Animal Science, Kazi Nazrul University, Asansol 713 340, West Bengal, India.
Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER), Berhampur 760 010, Odisha, India.
Infect Genet Evol. 2021 Jan;87:104633. doi: 10.1016/j.meegid.2020.104633. Epub 2020 Nov 9.
In spite of the tremendous efforts of the World Health Organization, scientific and medical community to eradicate lymphatic filariasis (LF) within 2020, the disease is still taking a huge toll on mankind throughout the globe. The current therapeutic strategies and solution measures against this alarming condition are suffering from a number of limitations such as inadequate effectiveness of the drugs against the adult-stage parasites, low bioavailability, and emergence of resistance. Considering this situation, development of the new therapeutics are urgently needed to combat human LF, especially targeting the adult filarial nematodes. Brugia malayi, the causative parasite for the human brugian filariasis majorly found in the countries of the South-Asia. In this study, we have designed a vaccine candidate using B-cell and T-cell epitopes derived from the aspartic protease of B. malayi (BmASP-1) and found to display significant humoral and cell mediated immune responses using in-silico approaches. Protein-protein docking between the human Toll-like receptor 4 (TLR4) and the vaccine candidate helped us to predict the way of inductive signaling that leads to immune-response. Molecular dynamics (MD) simulation studies further confirmed the proper docking between the TLR4 and vaccine candidate. Moreover, in-silico cloning of the vaccine element within the expression vector was found useful to optimize the restriction sites as well as to determine the primer location. Taken together, the in-silico vaccine candidate depicted in this study promises could be a useful therapeutic option for treating LF and experimental validation of this study is expected to strengthen the candidature of the said vaccine in the future.
尽管世界卫生组织、科学界和医学界为在 2020 年内消灭淋巴丝虫病（LF）做出了巨大努力，但该疾病仍在全球范围内给人类带来巨大的损失。目前针对这种令人担忧的疾病的治疗策略和解决方案措施存在许多局限性，例如药物对成虫阶段寄生虫的效果不足、生物利用度低以及出现耐药性等问题。考虑到这种情况，迫切需要开发新的治疗方法来对抗人类 LF，特别是针对成年丝虫。马来丝虫是导致人类班氏丝虫病的寄生虫，主要分布在南亚国家。在这项研究中，我们使用马来丝虫天冬氨酸蛋白酶（BmASP-1）的 B 细胞和 T 细胞表位设计了一种疫苗候选物，并通过计算机模拟方法发现其具有显著的体液和细胞介导的免疫反应。人类 Toll 样受体 4（TLR4）与疫苗候选物之间的蛋白-蛋白对接帮助我们预测了诱导免疫反应的诱导信号方式。分子动力学（MD）模拟研究进一步证实了 TLR4 和疫苗候选物之间的正确对接。此外，在表达载体中对疫苗元件进行计算机模拟克隆有助于优化限制酶切位点并确定引物位置。综上所述，本研究中描述的计算机模拟疫苗候选物有望成为治疗 LF 的一种有用的治疗选择，预计未来对这项研究的实验验证将增强该疫苗的候选资格。
