In this study, biodegradable cationic polycarbonate and polylactide block copolymers were synthesized and successfully used as novel vaccine adjuvants to provide enhanced anticancer immunity. The polymers formed nanoparticles with the model vaccine, ovalbumin (OVA), and the immunostimulant toll-like receptor 3 agonist poly(I:C) (a synthetic analog of the double-stranded RNA). Higher uptake of poly(I:C) by the bone marrow-derived dendritic cells and macrophages and OVA by dendritic cells was observed when delivered using the polymer adjuvant. In vivo experiments showed that these nanoparticles remained longer in the subcutaneous injection site as compared to OVA alone and led to higher production of anti-OVA specific antibodies with prolonged immunostimulation. When OVA was combined with poly(I:C) that was either co-entrapped in the same particles or as separate particles, a comparable level of anti-OVA IgG1 antibodies and interleukin-6 (IL-6) was produced in mouse blood plasma, and a similar level of cytotoxic T lymphocyte (CTL) response in mice was stimulated as compared to OVA/Alum particles. Furthermore, tumor rejection in the mice that were vaccinated for 9 months with the formulations containing the polymer adjuvant was stronger than the other treatment groups without the polymer. Notably, the cationic polycarbonates were not associated with any adverse in vivo effects. Thus, these biodegradable polymers may be promising substitutes for aluminum-based adjuvants in vaccine formulations.
Keywords: biodegradable adjuvants; cancer vaccine; immunization; ovalbumin; polymer adjuvants; vaccine nanocomplexes.