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Open AccessReview

Inflammasome-Mediated Immunogenicity of Clinical and Experimental Vaccine Adjuvants

The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Dublin D02 R590, Ireland
Kennedy Institute of Rheumatology Research, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Medical Sciences Division, University of Oxford, Oxford OX3 7FY, UK
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Vaccines 2020, 8(3), 554;
Received: 25 August 2020 / Revised: 16 September 2020 / Accepted: 18 September 2020 / Published: 22 September 2020
(This article belongs to the Special Issue Immunological Mechanisms of Vaccines and Adjuvants)
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. View Full-Text
Keywords: inflammasome; adjuvant; vaccine; immunogenicity; NLRP3; NLRC4; AIM2; pyrin; non-canonical; caspase-1 inflammasome; adjuvant; vaccine; immunogenicity; NLRP3; NLRC4; AIM2; pyrin; non-canonical; caspase-1
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Reinke, S.; Thakur, A.; Gartlan, C.; Bezbradica, J.S.; Milicic, A. Inflammasome-Mediated Immunogenicity of Clinical and Experimental Vaccine Adjuvants. Vaccines 2020, 8, 554.

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