Uses
Trehalose-6,6'-dibehenate is an orally active glycolipid. Trehalose-6,6'-dibehenate activates Mincle and inflammasome, inducing IL-1β secretion in a caspase activity-dependent manner. Trehalose-6,6'-dibehenate exerts a Myd88-dependent adjuvant activity. Trehalose-6,6'-dibehenate induces Th-1/Th-17 immune responses[1][2][3][4][5].
in vivo
Trehalose-6,6'-dibehenate (100 μg; i.p.; once) significantly reduced neutrophil recruitment in Nlrp3-deficient mice compared with wild-type mice in an in vivo inflammatory model experiment[2].
Trehalose-6,6'-dibehenate (250 μg DDA liposomes + 50 μg TDB per dose; subcutaneous injection; 2-3 times; two weeks apart) induced a strong Th-1/Th-17 response in mice immunized with the fusion protein Ag85B-ESAT6, and its adjuvant activity was strictly dependent on Myd88[3].
Trehalose-6,6'-dibehenate (present in DDA liposomes at different molar ratios (6.4-20 mol%); subcutaneous injection; 3 times; two weeks apart) was able to induce a strong and specific Th1-type immune response in female mice immunized with Ag85B-ESAT6, as evidenced by the production of a large amount of interferon-γ cytokine and high levels of IgG2b isotype antibodies[4].
Trehalose-6,6'-dibehenate (10 mg/kg. p.o., once a day, 7 days) activates Mincle in mice[5].
| Animal Model: | Female C57BL/6j mice (8-12 weeks old), immunization model with Ag85B-ESAT6 (0.01 mg/ml)[4] |
| Dosage: | DDA liposomes with different amounts of Trehalose-6,6'-dibehenate (TDB) (e.g., 250 μg DDA liposomes plus 25, 50 or 100 μg TDB per dose) |
| Administration: | Subcutaneous injection at the base of the tails three times, with a 2 - week interval between each immunization |
| Result: | Induced a strong, specific Th1-type immune response.
Produced high levels of IFN-γ and low levels of IL-5.
Elevated IgG2b antibody.
Showed an IgG2b/IgG1 ratio characteristic of a Th1 immune response.
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References
[1] Yu H, et, al. Chlamydia muridarum T-cell antigens formulated with the adjuvant DDA/TDB induce immunity against infection that correlates with a high frequency of gamma interferon (IFN-gamma)/tumor necrosis factor alpha and IFN-gamma/interleukin-17 double-positive CD4+ T cells. Infect Immun. 2010 May;78(5):2272-82. DOI:
10.1128/IAI.01374-09[2] Schweneker K, et al. The mycobacterial cord factor adjuvant analogue trehalose-6,6'-dibehenate (TDB) activates the Nlrp3 inflammasome. Immunobiology. 2013 Apr;218(4):664-73. DOI:
10.1016/j.imbio.2012.07.029[3] Althaus K. Mechanism of the adjuvant activity of the synthetic mycobacterial cord factor analog Trehalose-6, 6-dibehenate (TDB). Technische Universitt München, 2010.
[4] Davidsen J, et al. Characterization of cationic liposomes based on dimethyldioctadecylammonium and synthetic cord factor from M. tuberculosis (trehalose 6,6'-dibehenate)-a novel adjuvant inducing both strong CMI and antibody responses. Biochim Biophys Acta. 2005 Dec 10;1718(1-2):22-31. DOI:
10.1016/j.bbamem.2005.10.011[5] Ruizhi T A N, et al. Chaihuang Yishen Granules Improves Renal Fibrosis in Mice with Chronic Kidney Disease by Inhibiting Macrophagic Mincle. Traditional Chinese Drug Research & Clinical Pharmacology, 2023: 1658-1667.
[6] ALEXANDRA HUBER. Trehalose diester glycolipids are superior to the monoesters in binding to Mincle, activation of macrophages in vitro and adjuvant activity in vivo.[J]. Innate Immunity, 2016, 22 6: 405-418. DOI:
10.1177/1753425916651132[7] GÉRALD LARROUY-MAUMUS . Protective efficacy of a lipid antigen vaccine in a guinea pig model of tuberculosis[J]. Vaccine, 2017, 35 10: Pages 1395-1402. DOI:
10.1016/j.vaccine.2017.01.079
