Bacteria-Derived Micro/Nanoparticles for Vaccine Design

Abstract Vaccines have profoundly reduced the global burden of infectious diseases and are increasingly being explored for cancer immunotherapy. However, developing vaccine platforms capable of simultaneously achieving efficient antigen delivery, precise immune modulation, and durable protective immunity remains a major challenge. Bacteria-derived micro/nanoparticles (BPs) have recently emerged as promising vaccine platforms that integrate the structural advantages of nanomaterials with the intrinsic immunostimulatory properties of bacterial components. Their micro-to-nanoscale dimension, pathogen-mimicking architecture, and capacity for multivalent antigen presentation facilitate efficient lymphatic trafficking, antigen-presenting cell targeting, and coordinated activation of both innate and adaptive immunity. Moreover, the endogenous pathogen-associated molecular patterns (PAMPs) within BPs serve as built-in adjuvants, potentiating antigen cross-presentation, inducing trained immunity, and eliciting robust T-cell and B-cell responses. These unique structure–function relationships have accelerated the clinical translation of BP-based vaccines, with several candidates now in clinical trials or already commercialized. In this review, we discuss the fundamental mechanisms, engineering strategies, and clinical research progress of BPs in vaccine development, while critically emphasizing the current challenges in safety, mechanistic elucidation, and scalable manufacturing. We further outline future opportunities for harnessing BPs as precision-tailored platforms for next-generation immunization paradigms.