Vaccine efficacy can be increased by arraying immunogens in multivalent form on virus-like nanoparticles to enhance B-cell activation. However, the effects of antigen copy number, spacing and affinity, as well as the dimensionality and rigidity of scaffold presentation on B-cell activation remain poorly understood. Here, we display the clinical vaccine immunogen eOD-GT8, an engineered outer domain of the HIV-1 glycoprotein-120, on DNA origami nanoparticles to systematically interrogate the impact of these nanoscale parameters on B-cell activation in vitro. We find that B-cell signalling is maximized by as few as five antigens maximally spaced on the surface of a 40-nm viral-like nanoparticle. Increasing antigen spacing up to ~25–30 nm monotonically increases B-cell receptor activation. Moreover, scaffold rigidity is essential for robust B-cell triggering. These results reveal molecular vaccine design principles that may be used to drive functional B-cell responses.

通过在病毒样纳米颗粒上排列多价形式的免疫原以增强 B 细胞活化，可以提高疫苗效力。然而，抗原拷贝数、间距和亲和力以及支架呈递的维度和刚性对 B 细胞活化的影响仍然知之甚少。在这里，我们在 DNA 折纸纳米粒子上展示了临床疫苗免疫原 eOD-GT8，它是 HIV-1 糖蛋白-120 的工程外域，以系统地询问这些纳米级参数对体外 B 细胞活化的影响。我们发现，在 40 nm 病毒样纳米颗粒表面上最多间隔的五个抗原可以使 B 细胞信号最大化。将抗原间距增加到 ~25–30 nm 会单调增加 B 细胞受体的激活。而且，支架刚性对于强大的 B 细胞触发至关重要。这些结果揭示了可用于驱动功能性 B 细胞反应的分子疫苗设计原理。