Potentiating the Immune Responses of HBsAg-VLP Vaccine Using a Polyphosphoester-Based Cationic Polymer Adjuvant

[Image: see text] Virus-like particle (VLP)-based vaccines are required to be associated with a suitable adjuvant to potentiate their immune responses. Herein, we report a novel, biodegradable, and biocompatible polyphosphoester-based amphiphilic cationic polymer, poly(ethylene glycol)-b-poly(aminoethyl ethylene phosphate) (PEG–PAEEP), as a Hepatitis B surface antigen (HBsAg)-VLP vaccine adjuvant. The polymer adjuvant effectively bound with HBsAg-VLP through electrostatic interactions to form a stable vaccine nanoformulation with a net positive surface charge. The nanoformulations exhibited enhanced cellular uptake by macrophages. HBsAg-VLP/PEG–PAEEP induced a significantly higher HBsAg-specific IgG titer in mice than HBsAg-VLP alone after second immunization, indicative of the antigen-dose sparing advantage of PEG–PAEEP. Furthermore, the nanoformulations exhibited a favorable biocompatibility and in vivo tolerability. This work presents the PEG–PAEEP copolymer as a promising vaccine adjuvant and as a potentially effective alternative to aluminum adjuvants.