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MTP-PE Liposomes

Vaxjo ID 63
Vaccine Adjuvant Name MTP-PE Liposomes
Alternative Names MTP-PE Antigen presenting liposomes
Adjuvant VO ID VO_0001302
Description Liposomes containing the synthetic lipophilic analog of muramyl dipeptide, muramyl tripeptide phosphatidylethanolamine (MTP-PE), were used as adjuvants for the induction of humoral and cellular immune responses following immunization with protein or tumor antigens (Ullrich and Fidler, 1992).
Stage of Development Clinical Trial
Components N-acetyl-L-alanyl-D-isoglutaminyl-L-alanine-2-(1,2-dipalmitoyl-sn-glycero-3-(hydroxy-phosphoryloxy)) ethylamide, mono sodium salt (Vogel and Powell, 1995).
Molecular Weight MTP-PE, 1313.55
Appearance Lyophilized white powder.
Storage Store at 4° C for both the parent lyophilized compound and the liposome-formulated MTP-PE (Vogel and Powell, 1995).
Preparation In a study, Freeze-dried liposomes containing MTP-PE (CGP 19835A) and control liposomes were supplied by Ciba-Geigy Ltd. ( Summit, NJ) and reconstituted according to the procedure described by Kleinerman et al. [12]. Muramyl tripeptide phosphatidylethanolamine was incorporated into phospholipid liposomes composed of synthetic phosphatidylserine and phosphatidylcholine in a 3:7 molar ratio. The MTPPE: phospholipid ratio was 1:250 (mg/mg). Multilamellar liposomes containing MTP-PE were prepared from the lyophilized product by hydrating the lipids with 2 ml of HBSS for 2 mm and then vortexing for 5 mm. The liposome suspension consisted of 125 mg of phospholipid and 0.5 mg of MTP-PE for each milliliter of HBSS. Control liposomes, composed of synthetic phosphatidylserine and phosphatidylcholine in a 3:7 molar ratio, but devoid of MTP-PE, were resuspended in HBSS (Ullrich and Fidler, 1992).
Dosage In a study, the injection volume was adjusted so that each animal received protein mixed with various concentrations (50-200 ıg) of liposomal MTP-PE (Ullrich and Fidler, 1992).
Function In seronegative populations, humoral and cellular responses to HSV and HIV vaccine were not enhanced when MTP-PE was included in MF59. The addition of MTP-PE to the MF59-based HIV vaccine in HIV seropositive individuals resulted in a marked increase in HIV antigen lymphocyte proliferation (Vogel and Powell, 1995). Cellular immune reactions, including delayed-type hypersensitivity and lymphoproliferation in vitro, were observed following immunization of mice with a mixture of antigen and liposome-MTP-PE (Ullrich and Fidler, 1992).
Safety Liposome-formulated MTP-PE is currently under phase II/III trials. Some systemic toxicity with MTP-PE given with gp120 based HIVA vaccines. MTP-PE has been injected intravenously in a liposomal formulation in cancer patients and was safe up to 6 mg m 2 . Addition of MTP-PE to the MF59 adjuvant results in increased rates of local and systemic reactions over those seen in the absence of the muramyl peptide. No evidence of uveitis was seen in any patients receiving MF59 with MTP-PE (Vogel and Powell, 1995).
Related Vaccine(s)
References
Ullrich and Fidler, 1992: Ullrich SE, Fidler IJ. Liposomes containing muramyl tripeptide phosphatidylethanolamine (MTP-PE) are excellent adjuvants for induction of an immune response to protein and tumor antigens. Journal of leukocyte biology. 1992; 52(5); 489-494. [PubMed: 1431559].
Vogel and Powell, 1995: Vogel FR, Powell MF. A compendium of vaccine adjuvants and excipients. Pharmaceutical biotechnology. 1995; 6; 141-228. [PubMed: 7551218].