Specific antibody response towards predicted epitopes of the epidermal growth factor receptor induced by a thermostable synthetic peptide adjuvant conjugate

Abstract

Applying computer-assisted epitope prediction to the amino-acid sequence of the epidermal growth factor receptor (EGFR), the extracytoplasmic domain EGFR(516-529) was selected as a putative antigenic region. EGFR(516-529) was synthesized on a solid-phase matrix and N-terminally linked to the low mol. wt adjuvant tripalmitoyl-S-glyceryl-cysteinyl-serine (Pam3 Cys-Ser). The conjugation to this B cell and macrophage-activating lipopeptide considerably enhanced the immunogenicity of the EGFR peptide. Using the conjugate Pam3 Cys-Ser-EGFR(516-529), a peptide-specific monoclonal antibody was produced. By flow cytometry and immunoprecipitation the antibody was demonstrated to recognize EGFR on A431 cells, expressing large numbers of EGFR. With this novel approach synthetic immunogens can be prepared which could serve as thermostable synthetic vaccines with great potential in countries where a functional cold chain cannot be maintained.