Oxidized cholesterol-doped biomimetic pulmonary surfactant nanocarriers for enhanced pulmonary vaccine delivery

Pulmonary vaccines are considered to have the potential to trigger the respiratory immune system, closely mimicking the natural entry process of pathogens and providing strong viral protection. To improve the immunogenicity of pulmonary vaccines, we introduced a potent delivery system: bioinspired pulmonary surfactant nanocarriers (BPSNs) doped with oxidized cholesterol, specifically 7-ketocholesterol (7-KC). Our study revealed that these nanocarriers, leveraging natural lung surfactant lipids, precisely target lung macrophages with superb biocompatibility. The delivery of a broad-spectrum influenza HA antigen (HA@BPSN) and a ZBP1-activating adjuvant (CBL0137) (CBL@BPSN) via BPSNs, effectively elicited potent immune responses without impairing surfactant functions. Compared to clinically validated traditional inactivated vaccines and the MF59 adjuvant, HA@BPSN and CBL@BPSN induced nearly a 10-fold increase in antibody titers and significantly enhanced CD4⁺ and CD8⁺ T cell responses. This nanovaccine approach showcases superior, broad-spectrum immunoprotection against diverse influenza strains, underscoring BPSN's potential as an effective respiratory vaccine delivery platform and paving the way for refined vaccine design and personalized treatments.