Saihar Aisha, Yaseen Allah Rakha, Suleman Muhammad, Parveen Rukhsana, Bashir Hamid
Center for Applied Molecular Biology, CAMB, University of the Punjab, Lahore, Pakistan.
School of Biological Sciences, University of the Punjab, Lahore 54590, Pakistan.
Microb Pathog. 2025 Jan;198:107171. doi: 10.1016/j.micpath.2024.107171. Epub 2024 Nov 29.
Flaviviruses transmitted by arthropods, including the Murray Valley Encephalitis Virus (MVEV), are RNA viruses capable of causing severe encephalitis in various hosts. The spread of these viruses is closely linked to climatic conditions and the habitats of host and vector species, leading to outbreaks in new geographic regions. Notable encephalitis-causing flaviviruses include Japanese encephalitis virus (JEV), West Nile virus (WNV), and Kunjin virus (KUNV). MVEV, primarily spread by the mosquito Culex annulirostris and amplified by water birds such as egrets and Nankeen night herons, has caused significant outbreaks in Australia, including severe epidemics in 1951, 1956, and 1974. Despite its severity, no rapid diagnostic techniques or effective antiviral treatments are available, and current interventions are limited to supportive care and mosquito management. Given the absence of a licensed vaccine, this study aimed to develop a multi-epitope hybrid vaccine targeting MVEV using in silico approaches. The study focused on identifying B-cell and T-cell epitopes from the MVEV Envelope (E) protein, constructing a vaccine candidate, and computationally validating its immunogenic potential. The designed vaccine underwent rigorous analysis of its antigenic properties, allergenicity, and toxicity. Disulfide engineering and assessment of physicochemical properties ensured the structural integrity of the vaccine, supported by Ramachandran plot and ProSA web analyses. Molecular docking studies assessed the vaccine's binding affinities with TLR-3, and MHC-I. Population coverage analysis of MHC-I and MHC-II epitopes evaluated global efficacy. Additionally, molecular dynamics simulations explored the stability of docked complexes, and PDBsum analysis elucidated interaction details. Immunological simulations were conducted to predict immune response outcomes, providing comprehensive validation of the vaccine's antigenicity. The findings highlight the potential of a multi-epitope vaccine as a viable strategy for MVEV prevention.
由节肢动物传播的黄病毒，包括墨累谷脑炎病毒（MVEV），是能够在多种宿主中引起严重脑炎的RNA病毒。这些病毒的传播与气候条件以及宿主和媒介物种的栖息地密切相关，导致在新的地理区域爆发疫情。值得注意的引起脑炎的黄病毒包括日本脑炎病毒（JEV）、西尼罗河病毒（WNV）和库京病毒（KUNV）。MVEV主要由环喙库蚊传播，并由白鹭和黄斑夜鹭等水鸟扩增，在澳大利亚引发了重大疫情，包括1951年、1956年和1974年的严重流行。尽管其严重性，但目前尚无快速诊断技术或有效的抗病毒治疗方法，当前的干预措施仅限于支持性护理和蚊虫管理。鉴于缺乏许可疫苗，本研究旨在使用计算机方法开发一种针对MVEV的多表位杂交疫苗。该研究专注于从MVEV包膜（E）蛋白中鉴定B细胞和T细胞表位，构建候选疫苗，并通过计算机验证其免疫原性潜力。设计的疫苗对其抗原特性、致敏性和毒性进行了严格分析。二硫键工程和物理化学性质评估确保了疫苗的结构完整性，得到了拉氏图和ProSA网络分析的支持。分子对接研究评估了疫苗与TLR-3和MHC-I的结合亲和力。MHC-I和MHC-II表位的群体覆盖分析评估了全球效力。此外，分子动力学模拟探索了对接复合物的稳定性，PDBsum分析阐明了相互作用细节。进行了免疫模拟以预测免疫反应结果，为疫苗的抗原性提供了全面验证。研究结果突出了多表位疫苗作为预防MVEV的可行策略的潜力。
