Pulmonary mRNA-LNP vaccines for rapid and durable protection against bacterial infection.

Authors

Anqi Wei, Yu Miao, Zhou Yuan, Guanghui Li, Dexuan Lei, Yinyu Ma, Zhiwei Guo, Yuansong Sun, Tianhao Ding, Kaisong Tian, Qin He, Zui Zhang, Lianfeng Fan, Changyou Zhan, Xiaoli Wei

Published in

Nature communications. Jul 08, 2026. Epub Jul 08, 2026.

Abstract

Pulmonary bacterial infections remain a major clinical challenge. Although vaccination reduces infection rates and mortality, the vulnerable post-vaccination immunity gap can still result in infection and vaccine failure. In addition, effective vaccines are unavailable for many clinically important bacterial pathogens. Here, we report a pulmonary mRNA-lipid nanoparticle (mRNA-LNP) vaccine incorporating an ionizable lipid engineered for localized high-level expression, which elicits both rapid and durable protection against bacterial lung infections in female mice, effectively bridging this critical window of vulnerability. Intratracheal delivery of mRNA-LNP rapidly primes lung neutrophils and macrophages into a transcriptionally pre-activated state, enhancing their phagocytic activity and enabling rapid, antigen-independent bacterial clearance during the early post-vaccination period (approximately 1-7 days). Subsequently, vaccination induces potent antigen-specific adaptive responses, conferring sustained protection against both laboratory and clinical drug-resistant Pseudomonas aeruginosa strains. Single-cell transcriptomics and immune profiling reveal coordinated activation of innate and adaptive immune programs. This dual-phase immune response exemplifies a paradigm-shifting vaccine design that integrates innate and adaptive immunity to confer both immediate and long-term protection. Our findings establish a mechanistic basis for rapid antibacterial defense and highlight pulmonary mRNA-LNP vaccination as a promising strategy for combating respiratory infections.

PMID:
42420327
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.

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