Isoelectric Point at the Nano−Bio Interface Dictates the Humoral Immune Responses of Vaccine Adjuvants

Abstract

The isoelectric point is an intrinsic physicochemical property of nanoparticles that determines antigen adsorption and drug delivery efficacy. However, its impact on shaping immune responses remains poorly understood. Here, we engineered Alhydrogel adjuvants with tunable isoelectric points and systematically evaluated their immunological effects. Modulating the isoelectric point significantly influenced the adsorption of human papillomavirus (HPV)-like particles (VLPs), with adjuvants possessing slightly acidic isoelectric points producing significantly stronger humoral immune responses in mice. Mechanistic investigations showed that these adjuvants enhanced antigen uptake, accelerated antigen disappearance from the injection site, and increased CD80 expression on dendritic cells within draining lymph nodes. These identify the isoelectric point as a key regulator of adjuvant activity and establish a rational design principle for developing next-generation vaccine adjuvants with enhanced efficacy.