Data_Sheet_2_Computational Design of a Novel VLP-Based Vaccine for Hepatitis B Virus.docx

Hepatitis B virus (HBV) is a global virus responsible for a universal disease burden for millions of people. Various vaccination strategies have been developed using viral vector, nucleic acid, protein, peptide, and virus-like particles (VLPs) to stimulate favorable immune responses against HBV. Given the pivotal role of specific immune responses of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in infection control, we designed a VLP-based vaccine by placing the antibody-binding fragments of HBsAg in the major immunodominant region (MIR) epitope of HBcAg to stimulate multilateral immunity. A computational approach was employed to predict and evaluate the conservation, antigenicity, allergenicity, and immunogenicity of the construct. Modeling and molecular dynamics (MD) demonstrated the folding stability of HBcAg as a carrier in inserting Myrcludex and “a” determinant of HBsAg. Regions 1–50 and 118–150 of HBsAg were considered to have the highest stability to be involved in the designed vaccine. Molecular docking revealed appropriate interactions between the B cell epitope of the designed vaccine and the antibodies. Totally, the final construct was promising for inducing humoral and cellular responses against HBV.

乙型肝炎病毒（Hepatitis B virus, HBV）是一种全球性病原体，给全球数百万人带来了沉重的疾病负担。目前已开发出多种疫苗研发策略，依托病毒载体、核酸、蛋白、肽及病毒样颗粒（virus-like particles, VLPs）平台，以诱导针对HBV的保护性免疫应答。鉴于乙型肝炎表面抗原（hepatitis B surface antigen, HBsAg）与乙型肝炎核心抗原（hepatitis B core antigen, HBcAg）的特异性免疫应答在HBV感染防控中发挥关键作用，本研究将HBsAg的抗体结合片段插入HBcAg的主要免疫优势区（major immunodominant region, MIR）表位，设计了一款基于VLPs的疫苗，以诱导多维度免疫应答。本研究采用计算方法对该疫苗构建体的保守性、抗原性、变应原性及免疫原性进行预测与评估。建模与分子动力学（molecular dynamics, MD）分析证实，作为载体的HBcAg在插入Myrcludex与HBsAg的"a"抗原决定簇后，仍可保持良好的折叠稳定性。研究确定HBsAg的1–50与118–150区域稳定性最佳，可纳入该设计疫苗中。分子对接结果显示，所设计疫苗的B细胞表位与抗体间存在适宜的相互作用。综上，该最终疫苗构建体在诱导针对HBV的体液与细胞免疫应答方面具有良好应用潜力。