Table 1 Experimental stimulants, their immunological function, and dosage used
Immune stimulant | Agonist | Immune response | Dosage | |
|---|---|---|---|---|
1 | Class B CpG oligonucleotide | TLR9 agonist | Promotes activation and maturation of plasmacytoid DCs (pDCs) and stimulate small amount of INFα and IFNβ [63] Strongly activates B cells [64, 65] Induces secretion of IL-6, IL-10, IL-12 [66] | 5 μg/mL |
2 | Bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) (CDN) | STING Agonist | Increases production of IL-12, IFN-γ, IL-8, MCP-1, and RANTES Enhances T cell stimulatory activity [67] | 1 μg/mL |
3 | Flagellin from B. subtilis (FLA-BS) | Extracellular FLA-BS activation through TLR5 triggers MyD88- dependent-B activation, cytokine, and NO generation [70]. Detection of intracellular flagellin by NLRC4 and NAIP5 results in the formation of an inflammasome, which activates caspase-1 of IL-1β and IL-18 [71, 72]. | 100 ng/mL | |
4 | Lipopolysaccharides (LPSs) | TLR2 and TLR4 | Powerful T cell adjuvant that promotes clonal expansion of B cells, resistance to growth factor deprivation, and Th cell differentiation of activated T cells. Induces production of interlukin-1β (IL-1β), IL-6, IL-10, IL-12, and TNFα [73] | 1 μg/mL |
5 | Monophosphoryl-Lipid A (MPLA) | TLR 4 | Induces a strong Th1 response Promotes IFN-γ production by Ag- specific CD4 T cells [74] Enhance production of antigen-specific CD8 cytotoxic T lymphocytes [75] Induces production of IL-1β, IL-10, IL-6, IL-8, and TNF-α [73] | 1 μg/mL |
6 | Muramyl dipeptide (MDP) | NOD2 | MDP increases the production of IL-10 when coupled with TLR2 agonists [76] MDP’s potential stimulation of NLRP3 and NLRP1 produces IL-1β [77] Combining MDP with LTA (a TLR2 agonist) stimulates human monocyte derived DCs and increases TNF-α and IL-12 secretion [78] | 1 μg/mL |
7 | R848 | TLR7 and TLR 8 | R848 strongly induces cytokines such as TNF-α, IFNα, IL-12, and IFN-γ Helps in the induction of Th1 and Th2 cell types [79]. | 100 ng/mL |
8 | Polyanhydride NP | – | NP are readily phagocytosed by DCs, allow sustained release of antigen, and show a safe toxicological profile [80, 81] Induce T cell responses Has been shown to cause low inflammation [49] | 100 μg/mL |
9 | PBC Micelles | – | Micelles offer pH-responsive micellization and gelation to aid the antigen endosomal escape in a sustainable manner Induce B cell responses Has been shown to cause low inflammation [82] | 12.5 mg/mL |