Sharma Shivangi, Yadav Pragya D, Cherian Sarah
Indian Council of Medical Research (ICMR)-National Institute of Virology, Pune, Maharashtra, India.
Front Immunol. 2025 May 13;16:1535322. doi: 10.3389/fimmu.2025.1535322. eCollection 2025.
Nipah virus (NiV) is characterized by recurring outbreaks and causes severe neurological impact, leading to increased mortality rates. Despite the severity of the disease, there is no proven post-exposure treatment available, emphasizing the critical need for the development of an effective vaccine.
This study was aimed at designing a multi-epitope based vaccine candidate based on an in-silico approach.
NiV's Structural proteins were screened for B and T-cell epitopes, assessing characteristics like antigenicity, immunogenicity, allergenicity, and toxicity. Two vaccine constructs (NiV_1 & 2) were designed using different adjuvants (Cholera toxin and Beta-defensin 3) and linkers and their predicted 3D structures were evaluated for interaction with Toll-Like Receptor TLR-3 using docking and molecular dynamics (MD) simulation studies. Finally, The potential expression of the vaccine construct in Escherichia coli (E. coli.) was verified by cloning it into the PET28a (+) vector and immune simulations were undertaken.
The study identified 30 conserved, antigenic, immunogenic, non-allergenic, and non-toxic epitopes with a broad population coverage. Based on the stability of vaccine construct in MD simulations results, NiV_1 was considered for further analysis. immune simulations of NiV_1 indicated a substantial immunogenic response. Moreover, codon optimization and in-silico cloning validated the expressions of designed vaccine construct NiV_1 in E. coli.
The findings indicate that the NiV_1 vaccine construct has the potential to elicit both cellular and humoral immune responses. Additional and investigations are required to validate the computational observations.
尼帕病毒（NiV）具有反复爆发的特点，并会造成严重的神经影响，导致死亡率上升。尽管该疾病严重，但尚无经过验证的暴露后治疗方法，这凸显了开发有效疫苗的迫切需求。
本研究旨在基于计算机模拟方法设计一种基于多表位的候选疫苗。
对NiV的结构蛋白进行B细胞和T细胞表位筛选，评估其抗原性、免疫原性、致敏性和毒性等特征。使用不同的佐剂（霍乱毒素和β-防御素3）和连接子设计了两种疫苗构建体（NiV_1和NiV_2），并通过对接和分子动力学（MD）模拟研究评估其预测的三维结构与Toll样受体TLR-3的相互作用。最后，将疫苗构建体克隆到PET28a（+）载体中，验证其在大肠杆菌中的潜在表达，并进行免疫模拟。
该研究确定了30个保守、抗原性、免疫原性、无致敏性和无毒性的表位，具有广泛的人群覆盖范围。基于MD模拟结果中疫苗构建体的稳定性，选择NiV_1进行进一步分析。NiV_1的免疫模拟显示出强烈的免疫原性反应。此外，密码子优化和计算机克隆验证了设计的疫苗构建体NiV_1在大肠杆菌中的表达。
研究结果表明，NiV_1疫苗构建体有潜力引发细胞免疫和体液免疫反应。需要进一步的研究来验证这些计算观察结果。
