Gul Irfan, Hassan Amreena, Muneeb Jan Mohd, Akram Towseef, Haq Ehtishamul, Shah Riaz Ahmad, Ganai Nazir Ahmad, Ahmad Syed Mudasir, Chikan Naveed Anjum, Shabir Nadeem
Laboratory of Vaccine Biotechnology, Division of Animal Biotechnology, Faculty of Veterinary Sciences and Animal Husbandry, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, India.
Department of Biotechnology, University of Kashmir, Srinagar, India.
Front Vet Sci. 2023 Jan 13;9:1116400. doi: 10.3389/fvets.2022.1116400. eCollection 2022.
Infectious bursal disease virus is the causative agent of infectious bursal disease (Gumboro disease), a highly contagious immunosuppressive disease of chicken with a substantial economic impact on small- and large-scale poultry industries worldwide. Currently, live attenuated vaccines are widely used to control the disease in chickens despite their issues with safety (immunosuppression and bursal atrophy) and efficiency (breaking through the maternally-derived antibody titer). To overcome the drawbacks, the current study has, for the first time, attempted to construct a computational model of a multiepitope based vaccine candidate against infectious bursal disease virus, which has the potential to overcome the safety and protection issues found in the existing live-attenuated vaccines. The current study used a reverse vaccinology based immunoinformatics approach to construct the vaccine candidate using major and minor capsid proteins of the virus, VP2 and VP3, respectively. The vaccine construct was composed of four CD8 epitopes, seven CD4 T-cell epitopes, 11 B-cell epitopes and a Cholera Toxin B adjuvant, connected using appropriate flexible peptide linkers. The vaccine construct was evaluated as antigenic with VaxiJen Score of 0.6781, immunogenic with IEDB score of 2.89887 and non-allergenic. The 55.64 kDa construct was further evaluated for its physicochemical characteristics, which revealed that it was stable with an instability index of 16.24, basic with theoretical pI of 9.24, thermostable with aliphatic index of 86.72 and hydrophilic with GRAVY score of -0.256. The docking and molecular dynamics simulation studies of the vaccine construct with Toll-like receptor-3 revealed fair structural interaction (binding affinity of -295.94 kcal/mol) and complex stability. Further, the predicted induction of antibodies and cytokines by the vaccine construct indicated the possible elicitation of the host's immune response against the virus. The work is a significant attempt to develop next-generation vaccines against the infectious bursal disease virus though further experimental studies are required to assess the efficacy and protectivity of the proposed vaccine candidate .
传染性法氏囊病病毒是传染性法氏囊病（甘博罗病）的病原体，这是一种鸡的高度传染性免疫抑制疾病，对全球的小型和大型家禽业都有重大经济影响。目前，减毒活疫苗虽存在安全性问题（免疫抑制和法氏囊萎缩）和有效性问题（突破母源抗体滴度），但仍被广泛用于控制鸡的这种疾病。为克服这些缺点，本研究首次尝试构建一种基于多表位的针对传染性法氏囊病病毒的候选疫苗的计算模型，该模型有可能克服现有减毒活疫苗中发现的安全性和保护问题。本研究采用基于反向疫苗学的免疫信息学方法，分别使用病毒的主要衣壳蛋白和次要衣壳蛋白VP2和VP3构建候选疫苗。疫苗构建体由四个CD8表位、七个CD4 T细胞表位、十一个B细胞表位和一个霍乱毒素B佐剂组成，通过适当的柔性肽接头连接。该疫苗构建体经评估具有抗原性（VaxiJen评分为0.6781）、免疫原性（IEDB评分为2.89887）且无致敏性。对这个55.64 kDa的构建体进一步评估其理化特性，结果显示它很稳定，不稳定指数为16.24，呈碱性，理论等电点为9.24，热稳定，脂肪族指数为86.72，亲水性好，GRAVY评分为 -0.256。疫苗构建体与Toll样受体-3的对接和分子动力学模拟研究表明，两者具有良好的结构相互作用（结合亲和力为-295.94 kcal/mol）和复合物稳定性。此外，疫苗构建体对抗体和细胞因子的预测诱导表明，它可能引发宿主针对该病毒的免疫反应。这项工作是开发针对传染性法氏囊病病毒的下一代疫苗的一次重要尝试，不过还需要进一步的实验研究来评估所提出的候选疫苗的有效性和保护力。
