Table 1. Clinical development: vaccines/vaccine adjuvants/prophylactics.
| Toll-like receptor | Indication | Mechanism of action | Compound | Commercial name/company | Reference |
|---|---|---|---|---|---|
| TLR4 | Seasonal allergic rhinitis | Agonist | MPLA | Pollinex Quattro (Allergy Therapeutics)a | 30 |
| HBV | Adjuvant | AS04 and HBV antigen | FENDrix (GlaxoSmithKline)a | 31, 32 | |
| HSV, EBV | Adjuvant | AS04 | AS04 (GlaxoSmithKline)a | — | |
| Melanoma | Adjuvant | AS04 and cell wall products of Mycobacterium phlei | Enhanzyn | 33 | |
| Metastatic melanoma | Adjuvant | Enhanzyn and melanoma cell lysate | Melacinea | — | |
| HPV | Adjuvant | AS04 | Cervarixa | 34 | |
| Prostate cancer, non-small cell lung carcinoma | Adjuvant | AS04 and MUC1 tumor antigen | Stimuvax | — | |
| TB, VZV, HIV | Adjuvant | AS01 | — | — | |
| Malaria | Adjuvant | AS01 | Mosquirixa | 37 | |
| HBV | Adjuvant | Ribi.529 (lipid A mimetic) | Supervax | — | |
| Influenza (IAV), RSV, Malaria | Adjuvant | E6020 (lipid A mimetic) | E6020 (Eisai Pharmaceuticals) | 44 | |
| HSV, RSV | Adjuvant | lipid A derivative of MPLA in oil-in-water emulsion | GLA-SE IDRI | 45, 46, 47, 48 | |
| Neuropathic pain | Agonist | AV411 | Ibudilast | — | |
| Blood pressure | Antagonist | Peptide from vaccinia virus protein A46 | VIPER | 52 | |
| Asthma | |||||
| Rheumatoid arthritis | Antibody | NI-0101 | NI-0101 (Novimmunne)a | — | |
| Septic shock | Antagonist | Synthetic Lipopolysaccharide | Eritoran (Eisai Pharmaceuticals) | 49 | |
| TLR2 | Lime disease | Adjuvant | Pam3Cys linked to OspA of Borrelia burgdorferi | LYMErixa | 55 |
| HBV | Adjuvant | Palmitic acid conjugated to HBV core antigen | Theradigm-HBV | — | |
| HIV-1 | Adjuvant | Lipopeptides | — | 58 | |
| myocardial ischemia/reperfusion injury | Antibody | OPN-305 | OPN-305 (Opsona Therapeutics) | ||
| Cancer/anti-tumor models | Agonist | Components of Mycobacterium bovis BCG Tokyo | SMP105 (Dainippon Sumitomo Pharma) | 61 | |
| TLR3 | Influenza | Adjuvant | polyICLC /poly I:C12U (Ampligen) | FluMista | — |
| Chronic fatigue syndrome (CFS), hepatitis and HPV | Adjuvant | Ampligen | — | — | |
| TLR5 | myocardial ischemia/ reperfusion injury | Adjuvant | CBLB502 (synthetic flagellin) | Entolimod (Cleveland BioLabs) | 70 |
| Influenza | Adjuvant | Influenza antigen, M2e linked to Salmonella typhimurium flagellin. | VAX102 (VaxInnate) | 71 | |
| Influenza | Adjuvant | Influenza H1 hemagglutinin (HA) antigen linked to flagellin | VAX125 (VaxInnate) | 72 | |
| TLR7/8 | Basal cell and squamous cell carcinoma, lentigo maligna, actinic keratosis, HPV | Adjuvant | Imiquimod and Resiquimod | Aldarab | 74 |
| HSV, HIV and Leishmania infections | Adjuvant | Imiquimod | — | 75 | |
| Genital herpes | Adjuvant | Resiquimod | 3M Pharmaceuticals | — | |
| TLR9 | Tumors | Adjuvant | CpG–ODN | — | — |
| Melanoma vaccine Non-small-cell lung cancer | Adjuvant | CpG 7909 | ProMune/ Energix | — |
Abbreviations: AS01, MPLA, QS21 and liposomes; AS02, MPLA and QS21 in oil-in-water emulsion; AS04, MPLA, QS21 and alum; EBV, epstein-barr virus; HBV, hepatitis B virus; HPV, human pappilloma virus; HSV, herpes simplex virus; MPLA, monophospholipid A; RSV, respiratory syncytial virus; TB, tuberculosis; TLR, Toll-like receptor; VZV, varicella zoster virus.
a
Denotes adjuvants in clinical use.
b
In use for the topical treatment of HPV-induced warts.