In order to evoke an efficient immune response to prevent and eliminate infectious and malignant diseases, it is critical to develop more effective and safer vaccines or adjuvants to enhance the antigenicity of natural antigens. The objective of this study is to produce nanoparticles composed of poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA) and the model antigen ovalbumin (OVA), termed as p-OVAs, to assess the antigen sustained release property and the effectiveness in the immune responses in BALB/c mice. The results showed that the p-OVAs were spherical, evenly distributed with an average diameter of ∼290 nm, and had a sustained release property in vitro. After immunization of BALB/C mice with p-OVA, strong OVA-specific cellular and humoral immune responses were observed in vivo. The whole blood cell tests and histological results also suggested that immunization with p-OVA is both effective and relatively safe. Overall, here we provide new insight into future vaccine and/or adjuvant design with PVM/MA, which is promising for the immunotherapy of cancer and autoimmune diseases.