Cationic surfactant-dependent enhancement of antigen-specific cellular immunity by a biodegradable nanoparticle...

Infectious diseases remain a leading cause of morbidity and mortality worldwide and while antimicrobials play a crucial role in controlling infections, the rise of antimicrobial resistance (AMR) is a major global threat. Vaccination is key to prevent and treat diseases caused by resistant pathogens and there is a particular need for vaccines that induce strong T cell-mediated immunity. Nanoparticles comprised of biodegradable polymers, such as poly (lactic-co-glycolic acid) (PLGA), have shown promise due to their biocompatibility, controlled degradation, and capacity for surface modification. A particle size in the 50-60 nm range is beneficial to induce CD8⁺ T cell and Th1-biased responses. However, manufacturing such small PLGA nanoparticles with traditional approaches such as emulsification/solvent evaporation is challenging. Here, we addressed this challenge and formulated 50 nm polymeric nanoparticles using a modified nanoprecipitation method. We investigated the effect of a cationic surfactant in shaping adaptive immune responses. Nanoparticles stabilized using DOTAP and with a (50:50) PLA:PGA ratio were particularly effective in enhancing antigen-specific CD8⁺ T cells, CD4⁺ Th1 responses, and antigen-specific serum IgG titres. Notably, surfactant-free nanoparticles failed to elicit T cell responses and were less effective at enhancing antigen-specific antibodies, highlighting the crucial role of the cationic surfactant in promoting vaccine-induced adaptive immune responses. These findings were validated using ovalbumin (OVA) and Burkholderia pseudomallei outer membrane protein (BpOmpW) as antigens. Given that B. pseudomallei shows both intrinsic and acquired antibiotic resistance, this work underscores the potential of biodegradable polymeric nanoparticles as a promising platform for next-generation vaccines against AMR pathogens.