Sustained‐Release of Antigens and CpG‐DNA using Temperature‐Responsive Biodegradable Injectable Polymers: Performance on Induction of Immune Responses

Abstract

AbstractHere, a vaccine delivery system is developed that attains sustained release of antigens (ovalbumin; model antigen) and adjuvants (CpG‐DNA; oligodeoxynucleotides containing unmethylated cytosine‐guanine motifs) using biodegradable temperature‐responsive injectable polymers (IP). Previously a biodegradable IP system was prepared that exhibited a temperature‐responsive sol‐to‐gel transition and subsequent chemical cross‐linking. The IP system used triblock copolymers, poly(ε‐caprolactone‐co‐glycolide)‐b‐poly(ethylene glycol)‐b‐poly(ε‐caprolactone‐co‐glycolide) (tri‐PCG) and a polymer whose termini were converted to N‐hydroxysuccinimide esters (tri‐PCG‐OSu). OVA and CpG‐DNA sustained release was achieved using tri‐PCG‐based IP systems in vitro. Moreover, the release of CpG‐DNA was delayed using an IP system containing tri‐PCG‐OSu mixed with poly(L‐lysine) (PLL). Subcutaneous administration of the tri‐PCG‐based IP gel vaccine induced stronger humoral and cellular immune responses in mice than in those without IP administration. The Tri‐PCG‐OSu IP gel maintained high OVA‐specific IgG titers for 22 weeks. In contrast, the tri‐PCG IP gel exhibits a relatively rapid release of CpG DNA in vitro, predominantly inducing cellular immune responses. Furthermore, the tri‐PCG IP gel shows a potent antitumor effect against OVA‐expressing T lymphoma (E.G7‐OVA) and extends the survival duration of mice. Therefore, tri‐PCG‐based IP systems are promising vaccine platforms for controlling the release of antigens and adjuvants to enhance the humoral and cellular immune responses.