Aluminum hydroxide adjuvant induces macrophage differentiation towards a specialized antigen-presenting cell type

Rimaniol, Anne-Cécile; Gras, Gabriel; Verdier, F.; Capel, Francis; Grigoriev, V.; Porcheray, Fabrice; Sauzeat, Elisabeth; Fournier, Jean‐Guy; Clayette, Pascal; Siegrist, Claire‐Anne; Dormont, Dominique

doi:10.1016/j.vaccine.2004.01.061

Cited by 139 publications

(105 citation statements)

References 17 publications

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“…It is well known that alum injection results in cell recruitment to the injection site [7,8]. More recently, it was reported that alum activates human monocytes and macrophages in vitro [9][10][11][12]. Two independent reports have demonstrated that alum acts as an immunostimulator also in vivo.…”

Section: Proposed Mechanisms Of Action For Alummentioning

confidence: 99%

Alum adjuvanticity: Unraveling a century old mystery

2008

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The development of vaccine adjuvants for human use has been one of the slowest processes in the history of medicine. For almost one century, aluminium hydroxide (alum) has been the only vaccine adjuvant approved worldwide. Only in the past decade have two oil-inwater emulsions and one TLR agonist been approved by the European authorities as new vaccine adjuvants. Despite the fact that alum has been injected into billions of people, its mechanism of action is not fully understood. Recently, several reports have greatly increased our knowledge of the molecular and cellular events triggered by alum; however, the contribution of each of these processes to alum adjuvanticity is still unclear. A study published in this issue of the European Journal of Immunology, together with two recent publications, have demonstrated that the NOD-like receptor, pyrin domain containing 3 (Nlrp3)-inflammasome is the molecular target of alum immunostimulatory activity in vitro. Surprisingly, these three studies reported conflicting results on the requirement of the Nlrp3 inflammasome complex for alum adjuvant effects in vivo. This commentary attempts to resolve some of these discrepancies.

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Section: Proposed Mechanisms Of Action For Alummentioning

confidence: 99%

Alum adjuvanticity: Unraveling a century old mystery

2008

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“…It has been shown that alum adsorption increases antigen uptake by antigen-presenting cells (5). Alum alone is a weak activator of immune cells in vitro (6)(7)(8) but synergizes with LPS for the production of mature IL-1β through the activation of the Nlrp3 inflammasome complex (9)(10)(11). The activation of Nlrp3 in vitro has also been demonstrated for QuilA and chitosan, two other particulate adjuvants (11).…”

mentioning

confidence: 96%

Adjuvanticity of the oil-in-water emulsion MF59 is independent of Nlrp3 inflammasome but requires the adaptor protein MyD88

Seubert

Calabrό

Santini

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

161

127

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Oil-in-water emulsions have been successfully used to increase the efficacy, immunogenicity, and cross-protection of human vaccines; however, their mechanism of action is still largely unknown. Nlrp3 inflammasome has been previously associated to the activity of alum, another adjuvant broadly used in human vaccines, and MyD88 adaptor protein is required for the adjuvanticity of most Toll-like receptor agonists. We compared the contribution of Nlrp3 and MyD88 to the adjuvanticity of alum, the oil-in-water emulsion MF59, and complete Freund's adjuvant in mice using a threecomponent vaccine against serogroup B Neisseria meningitidis (rMenB). Although the basal antibody responses to the nonadjuvanted rMenB vaccine were largely dependent on Nlrp3, the highlevel antibody responses induced by alum, MF59, or complete Freund's adjuvant did not require Nlrp3. Surprisingly, we found that MF59 requires MyD88 to enhance bactericidal antibody responses to the rMenB vaccine. Because MF59 did not activate any of the Tolllike receptors in vitro, we propose that MF59 requires MyD88 for a Toll-like receptor-independent signaling pathway.

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“…14 In a recent study, the aluminium-containing Imject Ò (Pierce Biochemicals) adjuvant recruited and activated inflammatory monocytes to the site of injection through the induction of uric acid, 15 and in the presence of TLR agonists aluminium induces inflammasome activation. [16][17][18] Aluminium salts induce Th2 differentiation and humoral immunity, 19,20 but the exact mechanism, as well as the dependence on the classical Th2-inducing cytokine, interleukin (IL)-4, remains unclear both in vitro [21][22][23][24][25] and in vivo. 26,27 In this respect it is a problem that negative results are rarely published because this may lead to an erroneous bias in the general view of how aluminium salts function as adjuvants.…”

mentioning

confidence: 99%

T‐helper 1 and T‐helper 2 adjuvants induce distinct differences in the magnitude, quality and kinetics of the early inflammatory response at the site of injection

et al. 2009

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T-helper 1 and T-helper 2 adjuvants induce distinct differences in the magnitude, quality and kinetics of the early inflammatory response at the site of injection Introduction With the vast amount of information on T-cell differentiation that has been obtained in recent years, and in particular that on the role of pathogen-associated molecular patterns (PAMPs) in the induction of immune responses, it should in theory be possible to tailor vaccines and adjuvants to selectively induce cell-mediated/humoral and T-helper 1/T-helper 2 (Th1/Th2) responses. This would obviously have tremendous impact on the ongoing

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Aluminum hydroxide adjuvant induces macrophage differentiation towards a specialized antigen-presenting cell type

Cited by 139 publications

References 17 publications

Alum adjuvanticity: Unraveling a century old mystery

Alum adjuvanticity: Unraveling a century old mystery

Adjuvanticity of the oil-in-water emulsion MF59 is independent of Nlrp3 inflammasome but requires the adaptor protein MyD88

T‐helper 1 and T‐helper 2 adjuvants induce distinct differences in the magnitude, quality and kinetics of the early inflammatory response at the site of injection

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