Abstract
In modern vaccines, adjuvants can be sophisticated immunological tools to promote robust and long-lasting protection against prevalent diseases. However, there is an urgent need to improve immunogenicity of vaccines in order to protect mankind from life-threatening diseases such as AIDS, malaria or, most recently, COVID-19. Therefore, it is important to understand the cellular and molecular mechanisms of action of vaccine adjuvants, which generally trigger the innate immune system to enhance signal transition to adaptive immunity, resulting in pathogen-specific protection. Thus, improved understanding of vaccine adjuvant mechanisms may aid in the design of “intelligent” vaccines to provide robust protection from pathogens. Various commonly used clinical adjuvants, such as aluminium salts, saponins or emulsions, have been identified as activators of inflammasomes - multiprotein signalling platforms that drive activation of inflammatory caspases, resulting in secretion of pro-inflammatory cytokines of the IL-1 family. Importantly, these cytokines affect the cellular and humoral arms of adaptive immunity, which indicates that inflammasomes represent a valuable target of vaccine adjuvants. In this review, we highlight the impact of different inflammasomes on vaccine adjuvant-induced immune responses regarding their mechanisms and immunogenicity. In this context, we focus on clinically relevant adjuvants that have been shown to activate the NLRP3 inflammasome and also present various experimental adjuvants that activate the NLRP3-, NLRC4-, AIM2-, pyrin-, or non-canonical inflammasomes and could have the potential to improve future vaccines. Together, we provide a comprehensive overview on vaccine adjuvants that are known, or suggested, to promote immunogenicity through inflammasome-mediated signalling.
Highlights
In the development of modern vaccines, adjuvants play a pivotal role as they can enhance protective immunity and usually provide an improved safety profile in comparison to live attenuated vaccines [1].As early as 1924, Gaston Ramon described the first vaccine adjuvants, which enhanced the immune response to diphtheria and tetanus vaccines [2]
Adjuvants can primarily perform one or more of several functions [5]: (I) creating a depot effect to maintain the release of antigen at the site of injection, (II) boosting the secretion of cytokines and chemokines, (III) enhancing the recruitment of innate immune cells at the site of injection, (IV) stimulating antigen uptake by antigen presenting cells (APCs), (V) enhancing APC maturation/expression of major histocompatibility complex (MHC) class II and co-stimulatory molecules and migration to draining lymph nodes and, importantly, (VI) activating the inflammasome, which is the main focus of this review
Canonical inflammasomes recruit caspase-1 via the adaptor molecule ASC, which leads to proximity-induced auto-processing and activation of caspase-1, resulting in cleavage leads which to proximity-induced auto-processing and activation of caspase-1, resulting in cleavage of of pro-IL-1β and pro-IL-18 as well as the secretion of their mature forms
Summary
In the development of modern vaccines, adjuvants play a pivotal role as they can enhance protective immunity and usually provide an improved safety profile in comparison to live attenuated vaccines [1]. Different adjuvants have diverse modes of action (MoA) in promoting immunity (reviewed in [5]), the common feature is to foster activation of innate immune cells, such as dendritic cells (DCs), monocytes, macrophages or neutrophils in order to boost activation of T- and B-cells, which are able to mediate robust and long-lasting immunity against a specific pathogen.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
