|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1995 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1994 : ¥1,300,000 (Direct Cost : ¥1,300,000)
The infectious experiments by peptide vaccine conjugated with epitope of bacterial- or virus antigen are carried out, but the results of these attempts are not enough. It is well known that lipid A,lipopeptide, muramyldipeptide (MDP) as bacterial cell membrane constituents exhibit adjuvant effect on enhancement of nonspecific-antibody formation. Therefore, the relations between the antibody productive effect and biological activities such as mitogenicity, tumor necrosis factor (TNF) and production of nitrite oxide (NO) were examined. The research results are as fellows ;
1. Mitogenicity and TNF production by analogs of ester-, ether-, homoglycerol-, and cysteinyl glycerol-types of glycerol moiety in lipopeptide were compared. The cysteinyl glycerol-type showed most strong activity. Further, synthetic tetra- or penta-peptide bearing dipalmitoyl groups in the glycerol moiety was fully biologic active as natural lipopeptide, which has tripalmitoyl groups in the glycerol moiety. The appropr
iate number of carbon in the acyl group seems to be 14 or 16. Lipopeptide analogs displayd potent biologic activity, but MDP-analogs linked peptide did not.
2. A.lipopeptide conjugated with peptide, H- (Gly-Pro-Gly-Arg-Ala-Phe) _3-OH,as a part of amino acid sequences in epitope of gp120 in HIV was intraperitoneally administered into BALB/c mice on days 0,16, and46, the peptide specific-antibody titers in their sera by each compound were determined with ELISA.The lipopeptide analogs-immunizing sera, which were obtained on days 14,30,42,57, and 70, were detected high titers than that of peptide alone, suggesting that the lipoglycerol derivatives cause the enhancement of production for peptide specific-antibodies. The sera immunized by dipalmitoyl derivative induced high titers than that by monopalmitoyl derivative. These compounds showed potent mitogenic activity and NO inducible activity.
3. Lipid A analog (monosaccharide-type) linked with serine or asparagine exhibited the mitogenicity and TNF production, but lethal toxicity did not. Therefore, the study on specific-antibody production by analogs of lipid a linked epitope peptide also appears to be interest. Less