Current landscape and challenges in adjuvant and antigen delivery systems for vaccine

Vaccines have emerged as a prominent strategy for the prevention and treatment of diseases. Adjuvants, as immune enhancers and delivery systems, play a crucial role in improving the efficiency and effectiveness of vaccines. Adjuvants can be categorized into three groups based on their mechanisms: immune enhancers, delivery systems, and a combination of both. While aluminum salt-based adjuvants have been the long-standing choice for many commercial vaccines, the adjuvant landscape in FDA-approved vaccines has evolved. Emulsions, liposomes, virus-like particles (VLPs), and newer platforms have been integrated into specialized vaccine formulations. In the context of modern vaccine platforms, the need for optimized adjuvant-delivery systems is increasing. For messenger RNA (mRNA) vaccines, lipid nanoparticles (LNPs) serve as efficient delivery vehicles, enhancing mRNA stability and cellular uptake. Additionally, LNPs can also function as immune-activating adjuvants, which further enhance the immune response. Similarly, viral vector vaccines leverage adjuvants that improve immune activation, while DNA vaccines benefit from adjuvants that promote both antigen stability and uptake. Emerging systems, such as bacterial outer membrane vesicles (OMVs), programmable nanoparticles (responsive to pH, enzymes, or light), and cell membrane-coated systems (e.g., red blood cell or macrophage membranes), offer advanced ways to enhance vaccine delivery and immune responses. These systems also enable better targeting and control of immune activation, addressing challenges in immune memory and long-lasting vaccine efficacy. However, the development of adjuvant systems also faces safety concerns, including the potential for excessive immune activation and toxicity in certain populations. Overall, this review discusses the current and evolving landscape of adjuvant-delivery systems for vaccines, with an emphasis on systems that support diverse vaccine platforms and optimize immune balance, biocompatibility, and long-term immunity, crucial for the success of future vaccine development.