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Saponin Vaccine Adjuvant

Vaxjo ID 14
Vaccine Adjuvant Name Saponin Vaccine Adjuvant
Adjuvant VO ID VO_0001267
Description Saponins are well recognized as potent immune stimulators, but their applicability as vaccine adjuvants have been limited due to associated toxicity (Skene and Sutton, 2006).
Stage of Development Research
Components Saponins are identified in the root of Polygala senega L., a plant indigenous to the Canadian prairies, which display immunopotentiation activity to protein and viral antigens (Estrada et al., 2000).
Preparation Saponins, contained in the roots of P. senega plants grown in Saskatchewan, Canada, were extracted with methanol in Soxhlet apparatus. The extract was concentrated, freeze-dried and re-extracted with water and butanol saturated with water. The dried butanolic extract, dissolved in a minimal amount of chloroform: methanol: water (64:26:10, lower phase solvent), was further fractionated by flash chromatography on a silica (10–40 μm particle size, type H, Sigma, Chemical Co., St Louis, MO, USA) column (25 mm i.d.×60 cm length). Column was eluted with a stepwise gradient of ascending polarity of chloroform: methanol: water solvent (64:26:10, 60:30:10, 55:35:10, 50:40:10, lower phases) to ensure separation of saponins from compounds of similar polarity, and also to achieve separation of individual saponin compounds from saponin mixture (Liu et al., 2002).
Dosage According to a study, mice were injected iv with 0.04-0.4 mg of saponin (Nakamura and Mori, 1984).
Function The P. senega saponins increased specific antibody levels to the antigens in mice. In mice, there was a preferential increase of the IgG2a subclass, and upon in vitro secondary antigen stimulation, high IL-2 and IFN-γ levels were observed in spleen cell cultures from P. senega saponins-immunized animals. The saponins were tested for their toxicity by lethality in mice and were found to be less toxic at the same dose than their counterpart Quil A. The results of this study indicated the potential of P. senega saponins as vaccine adjuvants to increase specific immune responses (Estrada et al., 2000).
Safety The existence of many different saponins that vary in their chemical or biological activities may lead to unpredictable effects in vivo if their relative ratios cannot be controlled. 22 fractions in Quil A have been identified and is reported that adjuvant activity was present in at least 10 of those tested, including the four most abundant saponins, termed QS-7, 17, 18, and 21. Kersten described 23 fractions in Quil A, all of which had adjuvant activity but that differed in other biological properties such as cell lysis and toxicity (Sjölander et al., 1998).
Related Vaccine(s)
References
Coulter et al., 2003: Coulter A, Harris R, Davis R, Drane D, Cox J, Ryan D, Sutton P, Rockman S, Pearse M. Intranasal vaccination with ISCOMATRIX adjuvanted influenza vaccine. Vaccine. 2003; 21(9-10); 946-949. [PubMed: 12547607].
Estrada et al., 2000: Estrada A, Katselis GS, Laarveld B, Barl B. Isolation and evaluation of immunological adjuvant activities of saponins from Polygala senega L. Comparative immunology, microbiology and infectious diseases. 2000; 23(1); 27-43. [PubMed: 10660256].
Liu et al., 2002: Liu G, Anderson C, Scaltreto H, Barbon J, Kensil CR. QS-21 structure/function studies: effect of acylation on adjuvant activity. Vaccine. 2002; 20(21-22); 2808-2815. [PubMed: 12034108].
Nakamura and Mori, 1984: Nakamura S, Mori KJ. Effects of reticuloendothelial blockade on acute saponin poisoning in mice. Toxicology. 1984; 29(3); 235-242. [PubMed: 6695384].
Sjölander et al., 1998: Sjölander A, Cox JC, Barr IG. ISCOMs: an adjuvant with multiple functions. Journal of leukocyte biology. 1998; 64(6); 713-723. [PubMed: 9850152].
Skene and Sutton, 2006: Skene CD, Sutton P. Saponin-adjuvanted particulate vaccines for clinical use. Methods (San Diego, Calif.). 2006; 40(1); 53-59. [PubMed: 16997713].