Table 1.

PRR adjuvant candidates and their activation mechanism.

Adjuvant/Candidate	PRRs	Mechanisms	References
Licensed adjuvants
Alum	NLRP3	Enters the cells via phagocytosis Activates NLRP3 inflammasome to induce the cleavage of pro-caspase 1 into caspase 1 Induces production of DAMPs to activate NLRP3 inflammasome	[40,41,42]
MF59, AS03	–	Enter the cells via pinocytosis Activate NF-κB dependent pathway via MyD88 without activating TLR signaling pathway	[93]
MPLA (AS01)	TLR4	Enter the cells via endocytosis Induces mainly IRF-3 signaling pathway via TRIF Activate NLRP3 together with QS-21	[60, 110, 112, 113]
QS-21 (AS01)	–	Enter the cells via endocytosis Activate Spleen tyrosine kinase (Syk) Induces NF-κB signaling pathway Activate NLRP3 together with MPLA	[109, 112, 113]
CpG 1018	TLR9	Induces NF-κB signaling pathway via MyD88	[121]
Potential adjuvants
dsRNA (Poly (I:C), Poly (ICLC), Poly (IC12U), ARNAX)	TLR3	Induces mainly IRF-3 signaling pathway via TRIF	[9, 158, 165, 173]
ssRNA (R837/R848)	TLR7, TLR8	Induces NF-κB signaling pathway via MyD88	[178, 179]
CpG ODN (CpG7909, MGN1703), IC31	TLR9	Induces NF-κB signaling pathway via MyD88	[192, 193, 194, 197]
Flagellin	TLR5, NLRC4	Induces NF-κB signaling pathway via MyD88 Also activates NLRC4 inflammasome to induce the cleavage of pro-caspase 1 into caspase 1	[216, 218]