Scheme 1
Schematic illustration of inhalable hybrid nanovaccines (NVRBD-MLipo) with virus-biomimetic structure against SARS-CoV-2 infection. Nanovesicles are derived from genetically engineered 293T cell expressing RBD (NVRBD), which are further fused with pulmonary surfactant (PS)-biomimetic liposomes containing MPLA (MLipo) to yield NVRBD-MLipo. After inhalable vaccination, NVRBD-MLipo effectively enters alveolar macrophages (AMs) due to its PS-biomimetic property, and induces AMs activation through MPLA-activated TLR4/NF-κB signaling pathway. Furthermore, NVRBD-MLipo elicits T and B cells activation, as well as generates high level of RBD-specific IgG and secreted IgA (sIgA) with broad-spectrum neutralization activity against pseudoviruses, thus boosting protective mucosal immune and systemic immune responses