Abstract
Immune responses induced by natural infection and vaccination are known to be initiated by the recognition of microbial patterns by cognate receptors, since microbes and most vaccine components contain pathogen-associated molecular patterns. Recent discoveries on the roles of damage-associated molecular patterns (DAMPs) and cell death in immunogenicity have improved our understanding of the mechanism underlying vaccine-induced immunity. DAMPs are usually immunologically inert, but can transform into alarming signals to activate the resting immune system in response to pathogenic infection, cellular stress and death, or tissue damage. The activation of DAMPs and cell death pathways can trigger local inflammation, occasionally mediating adaptive immunity, including antibody- and cell-mediated immune responses. Emerging evidence indicates that the components of vaccines and adjuvants induce immunogenicity via the stimulation of DAMP/cell death pathways. Furthermore, strategies for targeting this pathway to enhance immunogenicity are being investigated actively. In this review, we describe various DAMPs and focus on the roles of DAMP/cell death pathways in the context of vaccines for infectious diseases and cancer.
Highlights
Through the course of history, fatal viral or bacterial infections have posed a threat to human health, and vaccines against these pathogens have been continuously developed
This review focuses on the role of damage-associated molecular patterns (DAMPs)/cell death in vaccine-induced immunity
Vaccines have advanced with technological progress, and the COVID-19 pandemic has necessitated the delivery of gene-based vaccines worldwide
Summary
Through the course of history, fatal viral or bacterial infections have posed a threat to human health, and vaccines against these pathogens have been continuously developed. In the 1960s, split and subunit vaccines, which were new inactivated formulations, were tested in children under more stringent safety criteria [3] These types of vaccines primarily contain the viral surface antigens such as hemagglutinin and neuraminidase instead of whole viruses, as the former can induce antibody responses. Several recent studies have reported that squalene emulsion-based vaccine adjuvants such as AddaVax and MF59 stimulate damage-associated molecular patterns (DAMPs) or cell death signaling pathways [8]. With respect to vaccine-induced immunity, certain vaccine adjuvants are known to induce DAMPs and initiate or intensify immunogenicity These adjuvants, referred to as DAMP adjuvants, include alum, oil-in-emulsion adjuvants, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), and saponin-based adjuvants. We will discuss the potential applications of DAMPs and cell death pathways as targets for the development of effective vaccines
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