Recent advances in experimental polyphosphazene adjuvants and their mechanisms of action

Vaccination continues to be a very important public health intervention to control infectious diseases in the world. Subunit vaccines are generally poorly immunogenic and require the addition of adjuvants to induce protective immune responses. Despite their critical role in vaccines, adjuvant mechanism of action remains poorly understood, which is a barrier to the development of new, safe and effective vaccines. In the present review, we focus on recent progress in understanding the mechanisms of action of the experimental adjuvants poly[di(carboxylatophenoxy)phosphazene] (PCPP) and poly[di(sodiumcarboxylatoethyl-phenoxy)phosphazene] (PCEP) (in this review, adjuvants PCPP and PCEP are collectively referred to as PZ denoting polyphosphazenes). PZs are high molecular weight, water-soluble, synthetic polymers that have been shown to regulate innate immune response genes, induce cytokines and chemokines secretion at the site of injection and, also, induce immune cell recruitment to the site of injection to create a local immune-competent environment. There is an evidence that as well as its role as an immunoadjuvant (that activate innate immune responses), PZ can also act as a vaccine carrier. The mechanism of action that explains how PZ leads to these effects is not known and is a barrier to the development of designer vaccines.