Comparison of lipopeptide-based immunocontraceptive vaccines containing different lipid groups.
We have previously shown that incorporating the lipid moiety dipalmitoyl-S-glyceryl cysteine (Pam2Cys) into peptide structures effectively adjuvants otherwise weak immunogens. In this study lipopeptides based on luteinising hormone releasing hormone (LHRH) as a B cell epitope, [B], were synthesised in tandem with a 17-residue T-helper epitope, [T], derived from the fusion protein of the morbillivirus canine distemper virus. In this way vaccine candidates with the structure [T]-[B] were produced. These peptides were then lipidated with different diacylated moieties. The acyl moieties used were: palmitic acid (C16) to give Pam2Cys, stearic acid (C18) to give Ste2Cys, lauric acid (C12) to give Lau2Cys and octanoic acid (C8) to give Oct2Cys. We compared the immunogenicities of these simple lipopeptides in BALB/c mice by measuring their ability to induce anti-LHRH antibodies and found that immunogenicity was dependent on the length of the alkane chains of the incorporated lipid moieties with the hierarchy C16=C18>C12>C8. The antibody levels elicited by the lipopeptides also correlated with their ability to inhibit the reproductive capability of female mice in fertility trials. Furthermore, the C16 lipopeptide was the most effective in activating dendritic cells, measured by up regulation of surface MHC Class II molecules, and also in activating NF-kappaB in a Toll-like receptor-2 (TLR2)-dependent manner.
Chua
Brendon Y
BY
Cooperative Research Centre for Vaccine Technology, Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Zeng
Weiguang
W
Lau
Yuk Fai
YF
Jackson
David C
DC
D000276:Adjuvants, Immunologic; D000818:Animals; D000906:Antibodies / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry / Q000276:immunology; D008055:Lipids / Q000737:chemistry; D008074:Lipoproteins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D022642:Vaccines, Contraceptive / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology
D000276:Adjuvants, Immunologic; D000906:Antibodies; D008055:Lipids; D008074:Lipoproteins; D016328:NF-kappa B; D010455:Peptides; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D022642:Vaccines, Contraceptive; D007987:Gonadotropin-Releasing Hormone