Optimization of physiological properties of hydroxyapatite as a vaccine adjuvant

Hayashi, Masayuki; Aoshi, Taiki; Kogai, Yasumichi; Nomi, Daisuke; Haseda, Yasunari; Kuroda, Etsushi; Kobiyama, Kouji; Ishii, Ken J.

doi:10.1016/j.vaccine.2015.11.059

Cited by 30 publications

(31 citation statements)

References 38 publications

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“…In addition, antigen-loaded particles also function as an antigen reservoir by the depot effect (Glenny et al, 1926). Size, surface charge, surface hydrophilicity/lipophilicity and antigen-adjuvant binding strength have all been demonstrated to be important for the adjuvant effect of particles (Hayashi et al, 2016a, Yan et al, 2013). Advax is a microparticle adjuvant comprised of delta inulin particles but unlike other particle adjuvants it does not require adsorption with an antigen to mediate its effects, since it still provides an adjuvant effect when administered 24 h prior to administration of the antigen (Saade et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines

et al. 2017

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Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF)-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs) and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.

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Section: Discussionmentioning

confidence: 99%

Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines

et al. 2017

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“…Il-1r −/− mice were purchased from The Jackson Laboratory. Generation of Ips-1 −/− , Nlrp3 −/− , Caspase1 −/− , Sting Gt/Gt (Tmem173 gt ), Irf3 −/− , Irf7 −/− , Tnfa −/− and Tbk1 −/− mice have been described previously 28 40 41 42 . All animal experimental protocols were approved by the Institutional Animal Care and Use Committee at the Japanese National Institute of Biomedical Innovation, and all animal experiments were performed in accordance with the Institutional Guidelines for the Japanese National Institute of Biomedical Innovation, Health and Nutrition Animal Facility.…”

Section: Methodsmentioning

confidence: 99%

RNA is an Adjuvanticity Mediator for the Lipid-Based Mucosal Adjuvant, Endocine

Hayashi

Aoshi

Ozasa

et al. 2016

Sci Rep

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Nasal vaccination has the potential to elicit systemic and mucosal immunity against pathogens. However, split and subunit vaccines lack potency at stimulating mucosal immunity, and an adjuvant is indispensable for eliciting potent mucosal immune response to nasal vaccines. Endocine, a lipid-based mucosal adjuvant, potentiates both systemic and mucosal immune responses. Although Endocine has shown efficacy and tolerability in animal and clinical studies, its mechanism of action remains unknown. It has been reported recently that endogenous danger signals are essential for the effects of some adjuvants such as alum or MF59. However, the contribution of danger signals to the adjuvanticity of Endocine has not been explored. Here, we show that RNA is likely to be an important mediator for the adjuvanticity of Endocine. Administration of Endocine generated nucleic acids release, and activated dendritic cells (DCs) in draining lymph nodes in vivo. These results suggest the possibility that Endocine indirectly activates DCs via damage-associated molecular patterns. Moreover, the adjuvanticity of Endocine disappeared in mice lacking TANK-binding kinase 1 (Tbk1), which is a downstream molecule of nucleic acid sensing signal pathway. Furthermore, co-administration of RNase A reduced the adjuvanticity of Endocine. These data suggest that RNA is important for the adjuvanticity of Endocine.

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“…A later study demonstrated that CaP crystals induce NLRP3-, ASC-, and caspase-1-dependent secretion of IL-1β in vitro [28]. However, antibody responses after immunisation with another form of calcium phosphate -hydroxyapatite -particles were shown to be independent of NLRP3, ASC and caspase-1, indicating that CaP particles might provide NLRP3 inflammasome-independent adjuvanticity in vivo [27].…”

Section: Nlrp3 Inflammasomementioning

confidence: 99%

“…Immunostimulating complex containing saponins, phospholipids and cholesterol NLRP3 [24,25] CpG-ODN TLR9 agonist (putative inflammasome-activator) NLRP3 [26] Ca 3 (PO 4 ) 2 Calcium phosphate NLRP3 [27,28] TDB Synthetic trehalose-6,6 -dibehenate (an analogue of mycobacterial cord factor trehalose-6,6 -dimycolate) NLRP3 [29,30] PLGA Poly(lactic-co-glycolic acid) microparticles NLRP3 [31] Table 1. Cont.…”

Section: Introductionmentioning

confidence: 99%

Inflammasome-Mediated Immunogenicity of Clinical and Experimental Vaccine Adjuvants

et al. 2020

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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.

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Optimization of physiological properties of hydroxyapatite as a vaccine adjuvant

Cited by 30 publications

References 38 publications

Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines

Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines

RNA is an Adjuvanticity Mediator for the Lipid-Based Mucosal Adjuvant, Endocine

Inflammasome-Mediated Immunogenicity of Clinical and Experimental Vaccine Adjuvants

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