Review Article

Adjuvants: Classification, Modus Operandi, and Licensing

Table 2

Adjuvants in clinical development (for details see https://www.clinicaltrials.gov/).

Adjuvant of clinical trialsTypeStudy phaseApplications

Alum203175 prophylactic1 Pilot, 109 Phase I, 16 Phase I/II, 31 Phase II, 4 Phase II/III, 11 Phase III, 3 Phase IVAllergy, anthrax, botulism, candidiasis, Campylobacter, Clostridium difficile, dengue, encephalitis, Helicobacter pylori, hepatitis b, Herpes simplex, hookworm infection, human papillomavirus, influenza, leishmaniasis, malaria, Meningococcus, Norovirus, Pneumococcus, poliomyelitis, Ross River virus, SARS, schistosomiasis, shigellosis, Staphylococcus, Streptococcus, West Nile virus, yellow fever
28 therapeutic8 Phase I, 5 Phase I/II, 13 Phase II, 2 Phase IIICocaine dependence, colorectal cancer, diabetes, HDL, HIV, hypertension, malaria, melanoma, myasthenia gravis, nicotine dependence, prostate cancer, rhinoconjunctivitis

Freund’s incomplete adjuvant1909 prophylactic4 Phase I, 1 Phase I/II, 2 Phase II, 2 Phase IIIBladder cancer, carcinoma, influenza, malaria, melanoma
181 therapeutic3 Pilot, 63 Phase I, 41 Phase I/II, 64 Phase II, 2 Phase II/III, 8 Phase IIIAcute myeloid leukemia, adenocarcinoma, bladder cancer, bile duct cancer, brain cancer, breast cancer, carcinoma, chronic myeloid leukemia, colorectal cancer, esophageal cancer, gastric cancer, glioblastoma, HIV, HPV-induced cancer, kidney cancer, liver cancer, melanoma, multiple myeloma, multiple sclerosis, non-small-cell lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, renal cell cancer

MF599392 prophylactic 27 Phase I, 6 Phase I/II, 34 Phase II, 3 Phase II/III, 16 Phase III, 6 Phase IVCytomegalovirus infections, influenza, HIV, respiratory syncytial virus
1 therapeutic1 Phase IHIV

Virosomes23 23 prophylactic8 Phase I, 1 Phase I/II, 1 Phase II, 9 Phase III, 4 Phase IVHepatitis A, Hepatitis C, influenza, malaria, vulvovaginal candidiasis

Virus-like particles10195 prophylactic19 Phase I, 6 Phase I/II, 31 Phase II, 36 Phase III, 3 Phase IVChikungunya, Enterovirus 71, HIV, human papillomavirus, influenza, malaria, Norovirus
6 therapeutic2 Phase I, 1 Phase I/II, 3 Phase IIHypertension, melanoma, respiratory syncytial virus

Poly(I:C) 161 prophylactic1 Phase I/IIInfluenza
15 therapeutic2 Pilot, 5 Phase I, 7 Phase I/II, 1 Phase IIAcute myeloid leukemia, allergy, breast cancer, glioblastoma, lymphoma, melanoma, non-small-cell lung cancer, ovarian cancer, prostate cancer

Poly-IC:LC563 prophylactic2 Phase I, 1 Phase IIColorectal cancer, HIV, melanoma
53 therapeutic6 Pilot, 19 Phase I, 17 Phase I/II, 11 Phase IIAcute myeloid leukemia, astrocytoma, bladder cancer, breast cancer, colorectal cancer, epithelial ovarian cancer, glioblastoma, glioma, HIV, low grade B cell lymphoma, melanoma, myeloma, non-small-cell lung cancer, pancreatic adenocarcinoma, prostate cancer

Monophosphoryl lipid A3122 prophylactic7 Phase I, 2 Phase I/II, 6 Phase II, 7 Phase IIIHepatitis B, Herpes simplex, HIV, hookworm infections, malaria, Norovirus, visceral leishmaniasis
9 therapeutic2 Phase I, 1 Phase I/II, 5 Phase II, 1 Phase IIIAllergic rhinitis, cutaneous leishmaniasis, melanoma, type I hypersensitivity

Flagellin66 prophylactic4 Phase I, 1 Phase I/II, 1 Phase IIDiarrhea, influenza, plague

Imiquimod403 prophylactic1 Phase II, 1 Phase II/III, 1 Phase IIIInfluenza, Hepatitis B, Varicella zoster
37 therapeutic2 Pilot, 20 Phase I, 2 Phase I/II, 9 Phase II, 2 Phase III, 2 Phase IVAdenocarcinoma of the prostate, basal cell carcinoma, brain tumor, breast cancer, cervical cancer, ependymoma, gastric cancer, glioblastoma, glioma, human papillomavirus, melanoma, non-small-cell lung cancer, ovarian cancer, prostate cancer, sarcoma

Resiquimod113 prophylactic2 Phase I, 1 Phase I/IIAllergic rhinitis, Hepatitis B, influenza
8 therapeutic2 Pilot, 1 Phase I, 2 Phase I/II, 3 Phase IIAdvanced malignances, bladder cancer, glioma, melanoma

CpG ODN96 prophylactic3 Phase I, 3 Phase I/IIBacterial sepsis, HIV, hookworm infection, malaria
3 therapeutic1 Phase I, 1 Phase I/II, 1 Phase IIAllergic rhinitis, breast cancer, Hepatitis B, HIV

Muramyl dipeptide11 prophylactic1 Phase IHIV

AS0322 22 prophylactic5 Phase I, 3 Phase I/II, 11 Phase II, 1 Phase III, 2 Phase IVDengue, influenza

AS043837 prophylactic2 Phase I, 6 Phase II, 27 Phase III, 2 Phase IVCervical cancer, Herpes simplex, human papillomavirus
1 therapeutic1 Phase II/IIIHepatitis B