Vaccine adjuvants: current status, research and development, licensing, and future opportunities.

Vaccines represent one of the most significant inventions in human history and have revolutionized global health. Generally, a vaccine functions by triggering the innate immune response and stimulating antigen-presenting cells, leading to a defensive adaptive immune response against a specific pathogen's antigen. As a key element, adjuvants are chemical materials often employed as additives to increase a vaccine's efficacy and immunogenicity. For over 90 years, adjuvants have been essential components in many human vaccines, improving their efficacy by enhancing, modulating, and prolonging the immune response. Here, we provide a timely and comprehensive review of the historical development and the current status of adjuvants, covering their classification, mechanisms of action, and roles in different vaccines. Additionally, we perform systematic analysis of the current licensing processes and highlights notable examples from clinical trials involving vaccine adjuvants. Looking ahead, we anticipate future trends in the field, including the development of new adjuvant formulations, the creation of innovative adjuvants, and their integration into the broader scope of systems vaccinology and vaccine delivery. The article posits that a deeper understanding of biochemistry, materials science, and vaccine immunology is crucial for advancing vaccine technology. Such advancements are expected to lead to the future development of more effective vaccines, capable of combating emerging infectious diseases and enhancing public health.