Improved vaccination requires better delivery of antigens and activation of the natural immune response. Here we report a lipid nanoparticle system with the capacity to carry antigens, including mRNA and proteins, which is formed into a virus-like structure by surface decoration with spike proteins, demonstrating application against SARS-CoV-2 variants. The strategy uses S1 protein from Omicron BA.1 on the surface to deliver mRNA of S1 protein from XBB.1. The virus-like particle enables specific augmentation of mRNAs expressed in human respiratory epithelial cells and macrophages via the interaction the surface S1 protein with ACE2 or DC-SIGN receptors. Activation of macrophages and dendritic cells is demonstrated by the same receptor binding. The combination of protein and mRNA increases the antibody response in BALB/c mice compared with mRNA and protein vaccines alone. Our exploration of the mechanism of this robust immunity suggests it might involve cross-presentation to diverse subsets of dendritic cells ranging from activated innate immune signals to adaptive immune signals.

改进的疫苗接种需要更好地输送抗原并激活自然免疫反应。在这里，我们报告了一种能够携带抗原（包括 mRNA 和蛋白质）的脂质纳米颗粒系统，该系统通过刺突蛋白的表面修饰形成病毒样结构，展示了针对 SARS-CoV-2 变体的应用。该策略在表面使用 Omicron BA.1 的 S1 蛋白来传递 XBB.1 的 S1 蛋白的 mRNA。这种病毒样颗粒能够通过表面 S1 蛋白与 ACE2 或 DC-SIGN 受体的相互作用，特异性增强人呼吸道上皮细胞和巨噬细胞中表达的 mRNA。巨噬细胞和树突细胞的激活是通过相同的受体结合来证明的。与单独使用 mRNA 和蛋白质疫苗相比，蛋白质和 mRNA 的组合增强了 BALB/c 小鼠的抗体反应。我们对这种强大免疫机制的探索表明，它可能涉及到不同树突细胞亚群的交叉呈递，从激活的先天免疫信号到适应性免疫信号。