Antibody-producing effects in mice by synthetic immunoactive lipopeptides with the conjugated amino acid sequence of gp120 in human immunodeficiency virus.
To induce peptide-specific antibodies in mice, as a model for vaccination against human immunodeficiency virus (HIV), lipopeptide analogs conjugated with three repeating units (KAB-112; designated as gp120-peptide) of a part (Gly-Pro-Gly-Arg-Ala-Phe) of the amino acid sequences of the V3 loop region in gp120 of HIV were synthesized. The mitogenicity, production of nitric oxide (NO) and induction of peptide-specific antibodies in mice by synthetic lipopeptides were examined. Compounds, KAB-8 (diacylglycerol-tetrapeptide having a part of the amino acid sequence in Escherichia coli), KAB-116 (diacylglycerol-cysteine), KAB-117 (diacylglycerol with gp120-peptide) and KAB-121 (KAB-8 with gp120-peptide) were capable of increasing significantly the incorporation of [3H]thymidine into splenocytes of C3H/He mice at concentrations ranging from 12.5 to 100 microM, but KAB-112 (gp120-peptide) and KAB-115 (monoacylglycerol with gp120-peptide) did not show such activity. The compounds, KAB-8, KAB-117 and 121, exhibited NO production in murine macrophages. When 50 nmol of these compounds was administered intraperitoneally into BALB/c mice on days 0, 16 and 46, the peptide-specific antibody titers in their sera produced by each compound were determined with ELISA. The sera of KAB-117 and KAB-121, which were obtained on days 14, 30, 42, 57 and 70, had a higher titer than that of KAB-112 and KAB-115, suggesting that the diacylglycerol derivative enhance the production of the peptide-specific antibodies.
Shimizu
T
T
University of Shizuoka, School of Pharmaceutical Sciences, Japan.
Iwamoto
Y
Y
Yanagihara
Y
Y
Ryoyama
K
K
Maruyama
Y
Y
Achiwa
K
K
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D004075:Diglycerides / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis*; D010446:Peptide Fragments / Q000737:chemistry*
D004075:Diglycerides; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); C104247:KAB 121; D010446:Peptide Fragments; D009569:Nitric Oxide