Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Cell Host Microbe. 2022 Jan 12;30(1):41-52.e5. doi: 10.1016/j.chom.2021.11.006. Epub 2021 Dec 7.
Respiratory syncytial virus (RSV) infection is a major cause of respiratory illness in infants and the elderly. Although several vaccines have been developed, none have succeeded in part due to our incomplete understanding of the correlates of immune protection. While both T cells and antibodies play a role, emerging data suggest that antibody-mediated mechanisms alone may be sufficient to provide protection. Therefore, to map the humoral correlates of immunity against RSV, antibody responses across six different vaccines were profiled in a highly controlled nonhuman primate-challenge model. Viral loads were monitored in both the upper and lower respiratory tracts, and machine learning was used to determine the vaccine platform-agnostic antibody features associated with protection. Upper respiratory control was associated with virus-specific IgA levels, neutralization, and complement activity, whereas lower respiratory control was associated with Fc-mediated effector mechanisms. These findings provide critical compartment-specific insights toward the rational development of future vaccines.
呼吸道合胞病毒（RSV）感染是婴儿和老年人呼吸道疾病的主要原因。尽管已经开发出几种疫苗，但由于我们对免疫保护相关性的理解不完整，这些疫苗都没有成功。虽然 T 细胞和抗体都发挥作用，但新出现的数据表明，仅抗体介导的机制可能足以提供保护。因此，为了绘制针对 RSV 的体液免疫相关性图谱，我们在高度受控的非人灵长类动物挑战模型中对六种不同疫苗的抗体反应进行了分析。在上呼吸道和下呼吸道都监测了病毒载量，并使用机器学习来确定与保护相关的与疫苗平台无关的抗体特征。上呼吸道的控制与病毒特异性 IgA 水平、中和作用和补体活性有关，而下呼吸道的控制与 Fc 介导的效应机制有关。这些发现为未来疫苗的合理开发提供了重要的、针对特定部位的见解。
