Table 3.
Clinical trials using Quillaja saponins as an adjuvant in vaccine formulations.
| Antigen | Adjuvant | Objective | Findings | Ref. |
|---|---|---|---|---|
| CHO-derived gp120 protein from HIV-1 | QS-21 or Al(OH)3 | Evaluate safety and assess kinetics of immune response | Improved T cell response inducing CTL activation with T helper cells was observed in formulations with QS-21. | [149] |
| Globo H-KLH (carbohydrate antigen found in most breast cancer cells) | QS-21 | Determine the formulation toxicity against cancerous cells, its immune response, and if the conjugation of Globo H with KLH would affect the immune response | Increase in specific antibody production and increased cytotoxicity either from complement system or antibody signaling. | [145] |
| PolySA and NP-polySA both conjugated with KLH (protein that in adults is associated with small cell lung cancer) | QS-21 | Determine the immune response after vaccination and assess the impact of polySA chemical manipulation | NP-polySA vaccination resulted in higher antibody titers with IgM response. The IgM was reactive to small cell lung cancer. | [146] |
| MUC-2G/Globo H-KLH | GPI-0100⬪; GPI-0100-P ⬪⬪; QS-21 | Present the use of GPI-0100 in humans and determine the safety and immunogenicity of a vaccine with different doses of GPI-0100. | GPI-0100 (5000 μg) and QS-21 (100 μg) produced comparable antibody titers. All adjuvanted vaccine doses were well tolerated and antigen-specific antibody titers matched increasing dose levels. | [83] |
| SL * | AS02A ⬪⬪⬪ | Evaluate the potential of an AS02A adjuvanted formulation in healthy individuals and compare it to a non-adjuvanted vaccine. | The adjuvanted vaccine induced more significative humoral and Th1 immune responses compared with the non-adjuvanted formulation. Despite the AS02A recipients reporting local and general reactions more frequently than the non-adjuvanted group, the safety profile was acceptable. | [153] |
| FMP1 ** | AS02A (oil-in-water formulation with mono- phosphoryl lipid A and QS-21 | Evaluate the safety and immunogenicity of malaria vaccine FMP1/AS02A in adults | FMP1 formulated with AS02A was well tolerated and showed high immunogenicity with specific anti-MSP-142 antibody titers boosted and prolonged due to the vaccination. | [147] |
| Influenza | QS-21 | Evaluate QS21 as an adjuvant and compare it with standard trivalent inactivated influenza | Local pain and post vaccination myalgias were greater in individuals that received QS-21. Despite increased serum antibodies, the mean titers for formulations (with or without QS-21) were not different. | [148] |
| RTS,S (recombinant proteins from P. falciparum) | AS02D | Evaluate the immunogenicity of RTS,S/AS02D formulation (liquid and lyophilized) | Lyophilized formulation is as efficient and safe as the liquid formulation, promoting satisfactory immunization. | [154] |
| PfAMA1 *** | AlhydrogelTM, Montanide ISA720 and AS02 Adjuvant System | Evaluate the immunogenicity and safety of PfAMA1 antigen (two different doses with three different adjuvants) | All formulations caused different reactogenicity with no serious reported adverse effects. All formulations tested induced antibody production, with AS02 being the most pronounced. | [155] |
| RTS,S **** | AS02A | Determine the safety of the RTS,S antigen formulated with AS02A adjuvant. | The formulation was well tolerated in children, with a good safety profile within the number of doses. The AS02A formulation caused fewer serious adverse events compared to the control group. | [156] |
| FMP2.1 ***** | AS02A | Evaluate the reactogenicity, safety, and immunogenicity of the malaria vaccine FMP2.1/AS02A in adults. | The formulation was well tolerated and showed good safety. Also, it was highly immunogenic. | [157] |
| No antigen was used | Quillaja saponins | Determine if dietary QS can modify macrophage activity and investigate its effects on liver function and inflammatory response | An increase in chemotactic and phagocytosis activities were observed. Furthermore, no adverse effects were seen since no significant changes in immunoglobulin, transaminase, IL-1α, and TNF- α were observed. | [144] |
| NP-polySA-KLH (Polysialic acid conjugated to keyhole limpet hemocyanin (KLH)) | QS-21 | Confirm the safety profile and determine the optimal dose | The lowest optimal immunogenic dose was 10 µg, which resulted in consistent high-titer antibody responses. | [151] |
| MAGE-A3 (tumor-specific protein usually expressed in melanoma) | AS02B or AS15 | Discover which adjuvant would cause a more robust and persistent immune response | AS15 provided a more robust immune response by activating more dendritic and B cells. | [152] |
| HBsAg (Hepatitis B virus surface antigen) | AS02B, AS02V, or AS01B | Evaluate the duration of humoral and cellular responses | All formulations induced persistent T CD4+ and CD8+ specific response, as well as B-cell response, indicating immunological memory. | [150] |
| Unimolecular conjugated Globo-H, GM2, sTn, TF, and Tf (markers usually expressed on ovarian cancer cell-surface) | QS-21 | Evaluate safety and immunogenicity of the pentavalent synthetic vaccine | 83% of individuals responded to at least three antigens with satisfactory immune response. | [158] |
| HBsAg (surface antigen of Hepatitis B virus), ovalbumin, CSP (P. falciparum circumsporozoite protein), and Varicella zoster glycoprotein E | AS01 | Investigate how combining immune-stimulants results in innate immune response | AS01 triggers innate response, such as NK-cells, and activates CD8 T-cells in the lymph nodes, depending on macrophage, IL-12, and IL-18. | [159] |
⬪ GPI-0100: Semi synthetic analogue of Quillaja saponin; ⬪⬪ GPI-0100P: GPI-0100 purified; ⬪⬪⬪ AS02A: oil-in-water formulation containing monophosphoryl lipid A and QS-21; * SL: recombinant hepatitis B protein containing the small protein (S) and the modified large (L) protein of the hepatitis B viral envelope, containing pre-Sl and pre-S2 sequences in addition to the entire S sequence. ** FMP1 (Falciparum malaria protein 1): recombinant protein based on the carboxy-terminal end of merozoite surface protein-1 (MSP-142) from the 3D7 clone of P. falciparum; *** PfAMA1: Plasmodium falciparum Apical Membrane Antigen; **** RTS,S: Plasmodium falciparum circumsporozoite surface antigen; ***** FMP2.1: recombinant protein (FMP2.1) based on Apical Membrane Antigen-1 (AMA-1) from the 3D7 clone of P. falciparum.