The development of a novel anti-peptoid antibody for a peptoid-based vaccine platform

Abstract Peptoids are synthetic molecules that share structure with peptides, but bear side groups on the backbone nitrogen. They are protease resistant and relatively cheap to synthesize. Since many amines can form peptoid side groups, peptoids are more diverse than peptides and can take on various shapes, making them good B cell epitopes or haptens. We aim to develop peptoid-based vaccines by screening on-bead peptoid libraries we have made with broadly neutralizing monoclonal antibodies against pathogens. Resulting peptoids can be attached to carrier proteins (which provide T cell epitopes) to elicit antibodies that should mimic the screening antibody. To test the immunogenicity of peptoid haptens, we generated the first affinity-purified anti-peptoid antibody by immunizing rabbits with a peptoid linked to a carrier and adsorbed to an adjuvant, alum. Antibodies were produced against the hapten, carrier and linker. After affinity purification, an enzyme-linked immunosorbent assay demonstrated a robust, specific response against the peptoid. This vaccine platform will now be applied using broadly neutralizing monoclonal antibodies against West Nile and hepatitis C viruses, mouse norovirus-1 and HIV. Candidate peptoids will be tested for the ability to induce neutralizing antibodies against the pathogen. If successful, this platform could be applied to any pathogen for which a broadly neutralizing monoclonal antibody is available, without structural knowledge of the native epitope.