CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, 11 Beiyitiao, Zhongguancun, Beijing, 100190, China.
Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China.
Nat Commun. 2024 Nov 6;15(1):9581. doi: 10.1038/s41467-024-53937-4.
Multivalent antigen display on nanoparticles can enhance the immunogenicity of nanovaccines targeting viral moieties, such as the receptor binding domain (RBD) of SARS-CoV-2. However, particle morphology and size of current nanovaccines are significantly different from those of SARS-CoV-2. Additionally, surface antigen patterns are not controllable to enable the optimization of B cell activation. Herein, we employ an icosahedral DNA origami (ICO) as a display particle for RBD nanovaccines, achieving morphology and diameter like the virus (91 ± 11 nm). The surface addressability of DNA origami permits facile modification of the ICO surface with numerous RBD antigen clusters (ICO-RBD) to form various antigen patterns. Using an in vitro screening system, we demonstrate that the antigen spacing, antigen copies within clusters and cluster number parameters of the surface antigen pattern all impact the ability of the nanovaccines to activate B cells. Importantly, the optimized ICO-RBD nanovaccines evoke stronger and more enduring humoral and T cell immune responses in female mouse models compared to soluble RBD antigens, and the multivalent display broaden the protection range of B cell responses to more mutant strains. Our vaccines activate similar humoral immunity, observable stronger cellular immunity and more memory immune cells compared to trimeric mRNA vaccines.
多价抗原在纳米颗粒上的展示可以增强针对病毒部分（如 SARS-CoV-2 的受体结合域（RBD））的纳米疫苗的免疫原性。然而，当前纳米疫苗的颗粒形态和大小与 SARS-CoV-2 有显著差异。此外，表面抗原模式不可控，无法优化 B 细胞激活。在此，我们采用二十面体 DNA 折纸（ICO）作为 RBD 纳米疫苗的展示颗粒，实现了与病毒相似的形态和直径（91±11nm）。DNA 折纸的表面可寻址性允许在 ICO 表面轻松修饰大量 RBD 抗原簇（ICO-RBD），形成各种抗原模式。通过体外筛选系统，我们证明了表面抗原模式的抗原间距、簇内抗原拷贝数和簇数参数都影响纳米疫苗激活 B 细胞的能力。重要的是，与可溶性 RBD 抗原相比，优化后的 ICO-RBD 纳米疫苗在雌性小鼠模型中引发更强和更持久的体液和 T 细胞免疫反应，而多价展示拓宽了 B 细胞反应的保护范围，使其对更多突变株具有保护作用。与三聚体 mRNA 疫苗相比，我们的疫苗激活了类似的体液免疫，可观察到更强的细胞免疫和更多的记忆免疫细胞。
