Table 1 The ‘known knowns’ and ‘known unknowns’ of adjuvants used in licensed vaccines
Adjuvant | Known knowns | Known unknowns |
|---|---|---|
Alum Aluminium hydroxide Aluminium phosphate | Antibody response independent of TLR signalling52 Activation of NLRP3 inflammasome in macrophages and DCs53,54 Activation of DCs is mediated by uric acid59 Rapid recruitment of neutrophils and formation of NETs62 Induces cell death that releases DNA, which triggers STING–IRF3 activation, necessary for IgE antibody and TH2 cell responsed62 | Innate receptors and signalling that result in antibody and T helper cell responses are poorly understood The relevance of stress response signals, tissue damage, and metabolic and nutrient sensing pathways is poorly understood There is conflicting evidence for a role of NLRP3 inflammasome in mediating adjuvant activity53,54,57 |
MF59 Squalene Tween (polysorbate) 80 Span 85 | Activates macrophages and DCs at injection site68 Induces chemokine secretion71 Antibody and CD4+ T cell responses depend on transient release of ATP by muscle cells73 TLR-independent MyD88 activation and NLRP3-independent ASC activation74,75 Stimulation of antigen-specific CD8+ T cells in tissues is via RIPK3-dependent pathway74 | Innate receptors and signalling that result in antibody and T helper cell responses are poorly understood The relevance of stress response signals, tissue damage, and metabolic and nutrient sensing pathways is poorly understood |
AS04 Alum MPL | Enhanced antigen presentation by AS04-activated DCs in comparison with alum78 TLR4 activation by MPL is critical and alum prolongs TLR4-induced responses78 | Innate receptors and signalling that sense alum and result in antibody and T helper cell responses poorly understood |
AS03 Squalence and α-tocopherol Tween (polysorbate) 80 | Induction of NF-κB activity and chemokine response locally and in draining lymph nodes in mouse between 6 and 48 h (ref.88) α-Tocopherol activates human monocytes and macrophages87 | Innate receptors and signalling that result in antibody and T helper cell responses are poorly understood The relevance of stress response signals tissue damage, and metabolic and nutrient sensing pathways is poorly understood |
AS01 MPL QS-21 Liposomes | Local secretion of chemokines, and IFNγ by NK cells and CD8+ T cells in draining LNs within hours101 QS-21 activates caspase 1 in SSMs98 Induces differentiation of monocytes to DCs213 Heterogeneous DC populations responsible for T cell activation in draining LNs213 | Innate receptors and signalling that sense QS-21 and result in antibody and T helper cell responses are poorly understood The relevance of stress response signals, tissue damage, and metabolic and nutrient sensing pathways is poorly understood |
CpG 1018 22-mer single-stranded DNA | Activates TLR9, which results in MyD88 pathway and type I interferon response | None |
