Effect of Hydrophobic Side Chains in the Induction of Immune Responses by Nanoparticle Adjuvants Consisting of Amphiphilic Poly(γ-glutamic acid)

The new generation vaccines are safe but,poorly immunogenic, and thus they require the use of adjuvants. Adjuvants that can control the balance and induction level of cellular and humoral immunities are urgently required for the treatment of and/or protection from infectious diseases and cancers. However, there are no adjuvants which can achieve these requirements. In this study, amphiphilic poly(gamma-glutamic-acid) (gamma-PGA) with various kinds of hydrophobic amino acid ethyl esters (AAE) was synthesized (gamma-PGA-AAE) and used to prepare antigen-encapsulated nanoparticles (NPs). gamma-PGA-graft-Leu (gamma-PGA-Leu, where Leu = leucine ethyl ester), gamma-PGA-graft-Phe (gamma-PGA-Phe, where Phe = phenylalanine ethyl ester), and gamma-PGA-graft-Tip (gamma-PGA-Trp, where Trp = tryptophan ethyl ester) formed monodispersed NPs that encapsulated ovalbumin (OVA). The type and the induction level of the antigen-specific cellular and humoral immunities could be controlled by the kinds of hydrophobic segments and vaccine formulation (encapsulation or mixture) used. When OVA was encapsulated into NPs, the cellular immunity was dominantly induced, while humoral immunity was dominant when OVA was mixed with NPs. These results are a first report to demonstrate that the balance and induction level of cellular and humoral immunities could be controlled by modifying compositions of NPs and vaccine formulation. Our results suggest that gamma-PGA-AAE NPs can provide safe and efficient nanoparticle-based vaccine adjuvants, and the results also provide guidelines in the rational design of amphiphilic polymers as vaccine adjuvants which can control the balance of immune responses.