Mast cell activators as adjuvants for intranasal mucosal vaccines

Mast cells have roles in immune regulation, allergy, and host response to pathogens. Compounds that activate mast cells (MCAs) can serve as vaccine adjuvants, potentially outperforming current FDA-approved options, especially for mucosal vaccines. While most vaccines are administered intramuscularly, intranasal and needle-free formulations offer benefits like improved compliance and accessibility. However, the lack of effective adjuvants limits mucosal vaccine development. This review explores MCAs as promising alternatives to traditional adjuvants, aiming to enhance mucosal vaccine efficacy. We summarize the nascent work of formulating MCAs like compound 48/80 into nanoparticles, with excipients such as chitosan and chitosan/alginate. Other MCAs like the peptide mastoparan 7 complexed with CpG have formed nanoparticle complexes that illustrate protective mucosal immunity in a model of influenza. The small molecule MCA ST101036, when encapsulated in acetalated dextran particles, has demonstrated enhanced immune responses and protection in a West Nile Virus model of infection. This review highlights the potential of MCAs as potent vaccine adjuvants, particularly for mucosal vaccines, and summarizes, recent advancements in formulating these activators into nanoparticles to enhance immune responses and protection.