Injectable Elastin-Like Polypeptide Hydrogel Depot System for Assessment of the Immune-Response-Inducing Efficacy of Sustained Antigen Release Alone

Abstract

Vaccines typically contain an antigen, delivery system (vehicle) and adjuvant, all of which contribute to the induction of a potent immune response. Consequently, design of new vaccines is difficult, because the contributions and interactions of these components are not easy to identify. Here, we aimed to develop an easy-to-use, immunologically inert, injectable depot system for sustained antigen release that would be suitable for assessing the efficacy of prolonged antigen exposure per se for inducing an immune response. This should mimic real-life infections. We selected recombinant elastin-like polypeptides with periodic cysteine residues (cELPs) as carriers and tetanus toxoid (Ttd) as an antigen. After subcutaneous injection of the mixture, cELP rapidly formed a disulfide cross-linked hydrogel in situ, within which Ttd is physically incorporated, affording a biodegradable antigen depot. We examined the stability and Ttd-release profile of a series of Ttd-containing hydrogels. A single injection induced high levels of tetanus antibody with high avidity for at least 20 weeks in mice. The chain length of cELP proved critical, whereas differences in hydrophobicity had little effect, although hydrophilic cELPs were more rapidly biodegraded. The ability of this system to separately identify the contribution of sustained antigen release to antibody induction should be helpful for rational design of next-generation vaccines.

Keywords: antigen depot, tetanus toxoid, antigen delivery, polypeptide, drug delivery