Highly immunogenic and totally synthetic lipopeptides as self-adjuvanting immunocontraceptive vaccines.
In this study, we describe the synthesis of various lipopeptides based on the sequence of luteinizing hormone-releasing hormone (LHRH) and report on their abilities to induce Abs against this "self" hormone when inoculated into mice in the absence of additional adjuvant. The peptides consisted of a colinear CD4(+) T helper cell epitope from the L chain of influenza virus hemagglutinin and LHRH, which has B cell epitopes but no T cell epitopes present in its sequence. Lipids were attached either at the N terminus or between the T cell epitope and LHRH, in the approximate center of the peptide. The lipopeptide constructs displayed different solubilities and immunological properties that depended not only on the lipid content but also on the position of attachment of the lipids. Some of these constructs were highly immunogenic, inducing high titers of Ab, which were capable of efficiently sterilizing female mice when administered in saline by s.c. or intranasal routes. The most effective vaccines were highly soluble, contained the dipalmitoyl-S-glyceryl cysteine moiety, and had this lipid attached at the center of the molecule. The relative ability of the lipopeptides to induce an Ab response in the absence of external adjuvant was reflected by their ability to up-regulate the surface expression of MHC class II molecules on immature dendritic cells. These results demonstrate that the composition and position within peptide vaccines of self-adjuvanting lipid groups can influence the ability to induce the maturation of dendritic cells and, in turn, the magnitude of the resulting Ab response.
Zeng
Weiguang
W
Cooperative Research Center for Vaccine Technology, Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
Ghosh
Souravi
S
Lau
Yuk Fai
YF
Brown
Lorena E
LE
Jackson
David C
DC
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000138:chemical synthesis*; D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007279:Injections, Subcutaneous; D008074:Lipoproteins / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012995:Solubility; D022642:Vaccines, Contraceptive / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008074:Lipoproteins; D022642:Vaccines, Contraceptive; D007987:Gonadotropin-Releasing Hormone; C038837:tripalmitoyl cysteine; D003545:Cysteine