Center for Cell and Virus Theory, Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Vaccine. 2013 Oct 1;31(42):4841-7. doi: 10.1016/j.vaccine.2013.07.075. Epub 2013 Aug 9.
Developing antiviral vaccines is increasingly challenging due to associated time and cost of production as well as emerging drug-resistant strains. A computer-aided vaccine design strategy is presented that could greatly accelerate the discovery process and yield vaccines with high immunogenicity and thermal stability. Our strategy is based on foreign viral epitopes engineered onto well-established virus-like particles (VLPs) and demonstrates that such constructs present similar affinity for antibodies as does a native virus. This binding affinity serves as one molecular metric of immunogenicity. As a demonstration, we engineered a preS1 epitope of hepatitis B virus (HBV) onto the EF loop of human papillomavirus VLP (HPV-VLP). HBV-associated HzKR127 antibody displayed binding affinity for this structure at distances and strengths similar to those for the complex of the antibody with the full HBV (PDBID: 2EH8). This antibody binding affinity assessment, along with other molecular immunogenicity metrics, could be a key component of a computer-aided vaccine design strategy.
由于生产相关的时间和成本以及新兴的耐药菌株，开发抗病毒疫苗的难度越来越大。本文提出了一种计算机辅助疫苗设计策略，该策略可以大大加快发现过程，并产生具有高免疫原性和热稳定性的疫苗。我们的策略是基于对已建立的病毒样颗粒（VLPs）进行工程改造的外来病毒表位，证明这些结构与天然病毒一样对抗体具有相似的亲和力。这种结合亲和力是免疫原性的一种分子衡量标准。作为一个演示，我们将乙型肝炎病毒（HBV）的 preS1 表位工程改造到人乳头瘤病毒 VLP（HPV-VLP）的 EF 环上。HBV 相关的 HzKR127 抗体与该结构的结合亲和力在距离和强度上与抗体与完整 HBV 的复合物（PDBID：2EH8）相似。这种抗体结合亲和力评估以及其他分子免疫原性指标，可能成为计算机辅助疫苗设计策略的关键组成部分。
