PEPTIDE POLYMERIZATION FACILITATES INCORPORATION INTO ISCOMS AND INCREASES ANTIGEN-SPECIFIC IGG2A PRODUCTION

Synthetic peptides can be tailor-made to include any B or T epitopes d esired from a single or multiple antigens or organisms. However, pepti des in general are not very immunogenic and have not proven easy to in corporate 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 respo nses in animals. Synthetic peptide ISCOM vaccines are few because of t he difficulty in incorporation of these peptides into ISCOMs. We have shown in this study, that non-immunogenic peptides could be made immun ogenic by polymerisation, and these polymers could be incorporated int o ISCOMs to give highly immunogenic vaccines. Synthetic 20mer peptides containing known B and T-helper epitopes from the E7 protein of the c ervical cancer associated human papillomavirus type 16 (HPV16 E7) have been used here as model immunogens. We have compared the humoral immu nity induced by these peptides as polymers or as copolymers with a lip id binding 20mer peptide (LAP 20), with or without incorporation into ISCOMs. Unpolymerised peptide elicited no measurable antibody. When po lymerised 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 weve pro duced For equal quantities of administered peptide (5 mu g), ISCOMs ga ve higher titres of antibody than CFA or PBS. Polymerised peptides ind uced high antigen-specific IgG2a:IgG1 ratios, which increased with mul tiple immunisations. These data indicate that polymerised peptides cou ld be incorporated into ISCOMS to form efficient immunogens which may elicit a Th1 type repsonse