Vol. 9, Issue 9, Part B (2025)

Outer membrane vesicles (OMVs) are nano-sized, spherical particles naturally released by Gram-negative bacteria through outer membrane blebbing. Composed of lipopolysaccharides (LPS), outer membrane proteins, phospholipids, and periplasmic components, OMVs play critical roles in bacterial communication, virulence, and host-pathogen interactions. Their intrinsic immunostimulatory properties and ability to deliver bioactive molecules have positioned OMVs as a powerful platform for vaccine development and drug delivery. This review comprehensively examines the bioengineering of OMVs for vaccine applications, focusing on their self-adjuvanting nature, antigen delivery capabilities, and potential in combating infectious diseases and cancer. We discuss strategies for modifying OMVs—including detergent extraction, genetic detoxification of LPS, and surface display of heterologous antigens—to enhance safety, immunogenicity, and targeting. The clinical success of OMV-based vaccines such as Bexsero® and PedvaxHIB highlights their translational potential. Furthermore, we explore the emerging role of OMVs in cancer immunotherapy, where they induce immunogenic cell death, promote trained immunity, and can be engineered to deliver chemotherapeutics or siRNA. Advances in scalable production and purification methods are also addressed, paving the way for broader clinical adoption. Collectively, OMVs represent a versatile and multifunctional platform that integrates antigen presentation, immune activation, and targeted delivery, making them a cornerstone of next-generation therapeutic and prophylactic strategies.