pH-triggered peptide self-assembly into fibrils: a potential peptide-based subunit vaccine delivery platform

Abstract

Background: Peptide-based subunit vaccines require strong adjuvants (immunostimulant) for therapeutic potency. There is strong demand for the discovery of new safe adjuvants and vaccine delivery systems that can be produced in a highly controlled manner. The pH dependent self-assembly of isopeptide derivatives into fibrils has been reported. Appropriately designed fibrils may have adjuvanting potency. Methods: Isopeptides conjugated to B-cell peptide epitopes (antigens) were synthesized. Properties of the resultant conjugates and their ability to undergo O-N intramolecular acyl migration reaction were analysed by HPLC, circular dichroism, and transmission electron microscopy. Results: The conjugates were converted to "parent" peptides via the pH-triggered O-N acyl migration reaction. The parent peptides aggregated into fibrils. The differences in conjugates composition resulted in different fibril morphology. Aggregation of produced peptides induced desired secondary conformation of antigens (peptide epitopes). Conclusions: The isopeptide approach presented herein may serve as a new self-adjuvanting delivery system for peptide-based vaccines. Such vaccines could be stable when stored in a non-aggregative form, and then converted on demand to the active form in pH-controlled manner. The use of a vaccine that is solely composed of endogenous components may reduce vaccine-associated side effects.