Adjuvants play an important role in vaccine efficacy by activating innate immune responses that effectively induce adaptive immunity. Since innate immune cells recognize pathogen-derived factors, such as pathogen-associated molecular patterns (PAMPs), through pattern recognition receptors and trigger inflammatory responses, PAMPs have been extensively exploited as vaccine adjuvants. However, accumulating evidence indicates that factors released from dying or stressed cells, collectively termed damage-associated molecular patterns, also activate innate immune cells and contribute to adjuvant immunogenicity. This review summarizes the molecular mechanisms of major forms of immunogenic cell death (ICD), including immunogenic apoptosis, pyroptosis, and necroptosis, and discusses their relevance to the mode of action of clinically approved and experimental vaccine adjuvants. Collectively, these findings support the concept of ICD as a promising platform for next-generation adjuvant development. A better understanding of cell death-driven immune activation will facilitate the rational design of adjuvants tailored to specific routes of administration, pathogens, and cancer types.
Adachi et al. (Wed,) studied this question.