title: Peptide polymerisation facilitates incorporation into ISCOMs and increases antigen-specific IgG2a production.
abstract: Synthetic peptides can be tailor-made to include any B or T epitopes desired from a single or multiple antigens or organisms. However, peptides in general are not very immunogenic and have not proven easy to incorporate into immunogenic vaccines. ISCOMs is an adjuvant system that has the capability not only to enhance the humoral immunogenicity of a protein but has also been shown to induce cell-mediated immune responses in animals. Synthetic peptide ISCOM vaccines are few because of the difficulty in incorporation of these peptides into ISCOMs. We have shown in this study that non-immunogenic peptides could be made immunogenic by polymerisation, and these polymers could be incorporated into ISCOMs to give highly immunogenic vaccines. Synthetic 20mer peptides containing known B and T-helper epitopes from the E7 protein of the cervical cancer associated human papillomavirus type 16 (HPV16 E7) have been used here as model immunogens. We have compared the humoral immunity induced by these peptides as polymers or as copolymers with a lipid binding 20mer peptide (LAP 20), with or without incorporation into ISCOMs. Unpolymerised peptide elicited no measurable antibody. When polymerised peptide was administered with CFA, or in phosphate-buffered saline (PBS) without adjuvant, or incorporated into ISCOMs, antibodies recognising both the immunising peptide and HPV16 E7 protein were produced. For equal quantities of administered peptide (5 micrograms), ISCOMs gave higher titres of antibody than CFA or PBS. Polymerised peptides induced high antigen-specific IgG2a:IgG1 ratios, which increased with multiple immunisations. These data indicate that polymerised peptides could be incorporated into ISCOMs to form efficient immunogens which may elicit a Th1 type response.
authors.affiliation: Papillomavirus Research Unit, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: G J
authors.initials: GJ
authors.lastname: Fernando
authors.forename: D J
authors.initials: DJ
authors.lastname: Stenzel
authors.forename: R W
authors.initials: RW
authors.lastname: Tindle
authors.forename: M S
authors.initials: MS
authors.lastname: Merza
authors.forename: B
authors.initials: B
authors.lastname: Morein
authors.forename: I H
authors.initials: IH
authors.lastname: Frazer
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000145:classification; D000918:Antibody Specificity; D001704:Biopolymers / Q000276:immunology; D004268:DNA-Binding Proteins; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D016882:ISCOMs / Q000737:chemistry / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000627:therapeutic use; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000276:immunology; D027383:Papillomaviridae / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D001704:Biopolymers; D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D000939:Epitopes; D016882:ISCOMs; D007074:Immunoglobulin G; D009856:Oncogene Proteins, Viral; D010455:Peptides