BACTERIAL DELIVERY SYSTEMS FOR IMMUNOGENIC PROTEINS: CURRENT ADVANCES, LIMITATIONS AND CHALLENGES
Bacterial platforms are emerging as versatile systems for delivering heterologous antigens and therapeutic proteins, driven by advances in microbial engineering and insights into host–pathogen interactions. This review summarizes recent peer-reviewed literature on bacterial delivery platforms, focusing on their mechanisms, immunological properties, applications, and limitations. Major approaches including live attenuated bacteria, secretion systems, surface display technologies, spores, outer membrane vesicles (OMVs), and bacterial ghosts (BGs) enable targeted intracellular or mucosal delivery and can elicit strong humoral, cellular, and innate immune responses. Live vectors naturally target antigen-presenting cells, while secretion systems such as the Type III secretion system (T3SS) allow precise cytosolic delivery. Spores provide stable, low-cost vehicles, and OMVs and BGs offer non-replicating particulate platforms with intrinsic adjuvanticity. Despite their potential, each system faces limitations, including low immunogenicity (spores), LPS toxicity and variability (OMVs, BGs), biosafety concerns (live vectors), and size or folding constraints (secretion and surface-display systems). Advancements in synthetic biology, immunomodulation, and scalable manufacturing are needed to overcome these barriers. Collectively, bacterial delivery platforms hold significant promise for next-generation vaccines and therapeutic protein delivery.