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Aiming to enhance the immunogenicity of subunit vaccines, a novel antigen delivery and adjuvant system based on dopamine polymerization on the surface of poly(d,l‐lactic‐glycolic‐acid) nanoparticles (NPs) with multiple mechanisms of immunity enhancement is developed. The mussel‐inspired biomimetic polydopamine (pD) not only serves as a coating to NPs but also functionalizes NP surfaces. The method is facile and mild including simple incubation of the preformed NPs in the weak alkaline dopamine solution, and incorporation of hepatitis B surface antigen and TLR9 agonist unmethylated cytosine‐guanine (CpG) motif with the pD surface. The as‐constructed NPs possess pathogen‐mimicking manners owing to their size, shape, and surface molecular immune‐activating properties given by CpG. The biocompatibility and biosafety of these pathogen‐mimicking NPs are confirmed using bone marrow …