Old and new adjuvants

McKee, Amy S.; Marrack, Philippa

doi:10.1016/j.coi.2017.06.005

Cited by 172 publications

(130 citation statements)

References 107 publications

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“…Intraperitoneal alum injection induces neutrophil infiltration in an IL‐1‐dependent and NLRP3‐independent fashion, whereas IL‐18 is not required for innate cell recruitment after intraperitoneal vaccination with alum . As neutrophil extracellular traps (NETs) are a source of chromatin and other alarmins, it was hypothesised that these could contribute to alum's adjuvanticity . A recent study by Stephen et al .…”

Section: Il‐1 Family Cytokines and Adjuvant Modes Of Actionmentioning

confidence: 99%

“…Moreover, instillation of alum in the lungs induces necrotic death of alveolar macrophages which results in IL‐1α release and formation of inducible bronchus‐associated lymphoid tissue in the lungs, Th2 responses and IgE production . Thus, it is possible that the IL‐1 family cytokines regulate alum‐induced responses in a tissue‐dependent manner which is dictated by the susceptibility of resident cells to alum‐induced necrosis . Alum‐containing human vaccines are administered intramuscularly but many mechanistic studies have used alternative routes, hence more research will be required to assess this context‐dependent contribution of IL‐1 family cytokines to alum‐induced humoral and cellular immunity.…”

Section: Il‐1 Family Cytokines and Adjuvant Modes Of Actionmentioning

confidence: 99%

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A Guide to IL‐1 family cytokines in adjuvanticity

Muñoz‐Wolf

Lavelle

2018

The FEBS Journal

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Growing awareness of the multiplicity of roles for the IL-1 family in immune regulation has prompted research exploring these cytokines in the context of vaccine-induced immunity. While tightly regulated, cytokines of the IL-1 family are normally released in response to cellular stress and in combination with other danger-/damage-associated molecular patterns (DAMPs), triggering potent local and systemic immune responses. In the context of infection or autoimmunity, engagement of IL-1 family receptors links robust innate responses to adaptive immunity. Clinical and experimental evidence has revealed that many vaccine adjuvants induce the release of one or multiple IL-1 family cytokines. The coordinated release of IL-1 family members in response to adjuvant-induced damage or cell death may be a determining factor in the transition from local inflammation to the induction of an adaptive response. Here, we analyse the effects of IL-1 family cytokines on innate and adaptive immunity with a particular emphasis on activation of antigen-presenting cells and induction of T cell-mediated immunity, and we address in detail the contribution of these cytokines to the modes of action of vaccine adjuvants including those currently approved for human use.

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Section: Il‐1 Family Cytokines and Adjuvant Modes Of Actionmentioning

confidence: 99%

Section: Il‐1 Family Cytokines and Adjuvant Modes Of Actionmentioning

confidence: 99%

A Guide to IL‐1 family cytokines in adjuvanticity

Muñoz‐Wolf

Lavelle

2018

The FEBS Journal

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“…This process might contribute to the adjuvant effect of alum. However, further confirmation is required [8]. In addition, alum induces a profound T helper 2 (Th2) response along with antibody production.…”

Section: Introductionmentioning

confidence: 99%

Cricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response

Kwak

Park

et al. 2019

Vaccine

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Keywords:MERS HPV CrPV IRES RNA Adjuvant Vaccine Th1/Th2 Alum a b s t r a c t An ideal adjuvant should increase vaccine efficacy through balanced Th1/Th2 responses and be safe to use. Recombinant protein-based vaccines are usually formulated with aluminum (alum)-based adjuvants to ensure an adequate immune response. However, use of alum triggers a Th2-biased immune induction, and hence is not optimal. Although the adjuvanticity of RNA has been reported, a systematic and overall investigation on its efficacy is lacking. We found that single strand RNA (termed RNA adjuvant) derived from cricket paralysis virus intergenic region internal ribosome entry site induced the expression of various adjuvant-function-related genes, such as type 1 and 2 interferon (IFN) and toll-like receptor (TLR), T cell activation, and leukocyte chemotaxis in human peripheral blood mononuclear cells; furthermore, its innate and IFN transcriptome profile patterns were similar to those of a live-attenuated yellow fever vaccine. This suggests that protein-based vaccines formulated using RNA adjuvant function as liveattenuated vaccines. Application of the RNA adjuvant in mouse enhanced the efficacy of Middle East respiratory syndrome spike protein, a protein-subunit vaccine and human papillomavirus L1 protein, a virus-like particle vaccine, by activating innate immune response through TLR7 and enhancing pAPC chemotaxis, leading to a balanced Th1/Th2 responses. Moreover, the combination of alum and the RNA adjuvant synergistically induced humoral and cellular immune responses and endowed long-term immunity. Therefore, RNA adjuvants have broad applicability and can be used with all conventional vaccines to improve vaccine efficacy qualitatively and quantitively.

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“…Механизм адъювантного дей-ствия алюминия остается до конца не изученным [11]. Вполне очевидно, что адъювантная активность препаратов алюминия проявляется в способности адсорбировать антигены, форми-ровать и медленно реализовывать депо антигенов, постепенно доставляя их в зоны локализации иммунокомпетентных клеток [12]. В свете накапливающихся современных данных механизм действия солей алюминия не может быть объяснен исключи-тельно классической теорией «депо».…”

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“…Другой возможный ме-ханизм -введение солей алюминия -способствует актива-ции системы комплемента, эозинофилов или макрофагов [11]. Известно также, что гидроксид алюминия способен вызывать продукцию цитокинов [9,12].…”

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