Table 1.
Mechanisms of action of adjuvants licensed for human use.
| Adjuvants | Proposed mechanisms of action | Immune response activated | Licensed vaccines | Reference |
|---|---|---|---|---|
| Alum | No depot effect | ↑ Ab responses | Many human vaccines (e.g., DTap, Hib, Hepatitis A, Hepatitis B) |
Gavin et al. (2006), Franchi and Nùñez (2008), Kool et al. (2008a), McKee et al. (2009), Hutchison et al. (2012) |
| NLRP3 activation in vivo? | ||||
| Independent of TLR signaling | ||||
| ↑ Local cytokines and chemokines | ↑ Th2 responses | |||
| ↑ Cell recruitment (eosinophils, monocytes, macrophages) | Poor Th1 responses | |||
| ↑ Ag presentation | ||||
| MF59 | No depot effect | Balanced Th1 and Th2 responses | Licensed for influenza vaccine (Fluad®), H5N1 pre-pandemic vaccine (Aflunov®), H1N1 pandemic vaccines (Focetria® and Celtura®) | Dupuis et al. (1999), Mosca et al. (2008), Calabro et al. (2011), Ellebedy et al. (2011) |
| NLRP3 independent but ASC-dependent | ||||
| Independent of TLR signaling but MyD88-dependent for Ab responses | ||||
| ↑ Local cytokines and chemokines | ||||
| ↑ Cell recruitment (neutrophils, macrophages, and monocytes) | ||||
| ↑ Ag uptake | ||||
| Activate muscle cells | ||||
| ↑ Ag-loaded neutrophils and monocytes in dLNs | ||||
| AS04 | MPL signals through TLR4 to activate APCs | ↑ Ab responses | Licensed for human papilloma virus (HPV) (Cervarix™), hepatitis B virus (Fendrix®) | Didierlaurent et al. (2009) |
| ↑ Local cytokines and chemokines | ||||
| ↑ Cell recruitment (DCs and monocytes) | ↑ Th1 responses | |||
| ↑ Ag-loaded DCs and monocytes in dLNs | ||||
| AS03 | Spatio-temporal co-localization with Ag | ↑ Ab responses | Licensed for pandemic flu vaccine (Pandemrix®) | Morel et al. (2011) |
| Transient ↑ cytokines locally and in dLNs | ||||
| ↑ Cell recruitment (granulocytes and monocytes) | ↑ Immune memory | |||
| ↑ Ag-loaded monocytes in dLNs | ||||
| Virosomes | Ag delivery vehicle | ↑ Ab responses | Licensed for Inflexal® V and Invivac® influenza vaccine and hepatitis A vaccines (Epaxal®) | Glück et al. (1992), Bungener et al. (2002a,b), Khoshnejad et al. (2007) |
| Bind APCs and induce receptor-mediated endocytosis | ↑ CTL responses | |||
| Escape endosomal degradation | ||||
| Ag presentation via MHC class II and MHC class I to CD4+ T cells and CD8+ T cells respectively | ||||
| Immunopotentiator |
Ab, antibody; Ag, antigen; CTL, cytotoxic T lymphocytes; dLNs, draining lymph nodes.