Totally synthetic lipid-containing polyoxime peptide constructs are potent immunogens.
A synthetic peptide corresponding to a sequence from influenza hemagglutinin was used as a model antigen to study the immunogenicity of polyoxime constructs. In the absence of any adjuvant, tetrameric forms of different polyoxime constructs did not elicit an antibody response. High and long-lasting levels of antibody were induced, however, by polyoxime constructs to which Pam3Cys (tripalmitoyl-S-glyceryl cysteine) was attached. Comparable serum antibody levels were achieved with Tetraoxime-Pam3Cys administered by the intraperitoneal or intranasal routes to those obtained when the monomeric peptide was administered by the intraperitoneal route in complete Freund's adjuvant (CFA). Mice receiving Tetraoxime-Pam3Cys and Pam3Cys-peptide intranasally developed peptide-specific antibody secreting cells (ASCs) in their lungs and mediastinal lymph nodes. At low dose, the Tetraoxime-Pam3Cys induced higher levels of antibody compared to those elicited by the monomeric Pam3Cys-peptide delivered by either route. These results show that lipo-tetraoxime constructs assembled by polyoxime chemistry can be potent inducers of systemic and mucosal immunity.
Zeng
W
W
Cooperative Research Centre for Vaccine Technology, Department of Microbiology and Immunology, The University of Melbourne, Parkville, Australia.
Jackson
D C
DC
Murray
J
J
Rose
K
K
Brown
L E
LE
D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D007114:Immunization; D007274:Injections, Intraperitoneal; D008055:Lipids / Q000276:immunology*; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010091:Oximes / Q000276:immunology*; D010455:Peptides / Q000276:immunology*
D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008055:Lipids; D010091:Oximes; D010455:Peptides