Antanasijevic Aleksandar, Schulze Autumn J, Reddy Vijay S, Ward Andrew B
Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
International AIDS Vaccine Initiative Neutralizing Antibody Center, Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
PNAS Nexus. 2022 Nov 4;1(5):pgac253. doi: 10.1093/pnasnexus/pgac253. eCollection 2022 Nov.
Non-polio enteroviruses (NPEVs) cause serious illnesses in young children and neonates, including aseptic meningitis, encephalitis, and inflammatory muscle disease, among others. While over 100 serotypes have been described to date, vaccine only exists for EV-A71. Efforts toward rationally designed pan-NPEV vaccines would greatly benefit from structural biology methods for rapid and comprehensive evaluation of vaccine candidates and elicited antibody responses. Toward this goal, we introduced a cryo-electron-microscopy-based approach for structural analysis of virus- or vaccine-elicited polyclonal antibodies (pAbs) in complex with whole NPEV virions. We demonstrated the feasibility using coxsackievirus A21 and reconstructed five structurally distinct pAbs bound to the virus. The pAbs targeted two immunodominant epitopes, one overlapping with the receptor binding site. These results demonstrate that our method can be applied to map broad-spectrum polyclonal immune responses against intact virions and define potentially cross-reactive epitopes.
非脊髓灰质炎肠道病毒（NPEV）可导致幼儿和新生儿患上严重疾病，包括无菌性脑膜炎、脑炎和炎性肌肉疾病等。尽管迄今为止已描述了100多种血清型，但仅存在针对EV - A71的疫苗。合理设计的泛NPEV疫苗的研发工作将极大地受益于结构生物学方法，以便对候选疫苗和引发的抗体反应进行快速而全面的评估。为实现这一目标，我们引入了一种基于冷冻电子显微镜的方法，用于分析与完整NPEV病毒粒子结合的病毒或疫苗引发的多克隆抗体（pAb）的结构。我们利用柯萨奇病毒A21证明了该方法的可行性，并重建了与该病毒结合的五种结构不同的pAb。这些pAb靶向两个免疫显性表位，其中一个与受体结合位点重叠。这些结果表明，我们的方法可用于绘制针对完整病毒粒子的广谱多克隆免疫反应图谱，并确定潜在的交叉反应表位。
