Nanovaccination Against Pseudomonas aeruginosa: Immune Mechanisms, Antigen Design Strategies, and Nanocarrier Platforms

Multidrug-resistant (MDR) Pseudomonas aeruginosa (PA) poses a formidable global public health threat, primarily due to its extensive antimicrobial resistance, diverse virulence mechanisms, propensity to form robust biofilms, and ability to evade immune clearance, particularly in respiratory infections. In recent decades, the delivery of multivalent antigens and the effectiveness of immune activation have both been greatly enhanced by nanovaccines. This review aims to elucidate recent advances in PA nanovaccines. We categorize innovative antigen design strategies for PA vaccines and highlight five major nanocarrier platforms used in PA nanovaccines: biodegradable polymeric nanocarriers, lipid-based nanocarriers, self-assembling protein nanoparticles, inorganic nanocarriers, and biomimetic nanocarriers. We emphasize how their unique physicochemical properties enhance targeted antigen delivery and antigen-presenting cell (APC) reprogramming, and summarize the self-adjuvanting properties exhibited by specific nanocarrier platforms. Finally, we discuss the major barriers to clinical translation of PA nanovaccines and potential strategies to overcome them, providing perspectives on antigen design strategies and functional expansion of future PA nanovaccines.