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Objective(s): Bacillus anthracis is the cause of the fatal anthrax. Available anthrax vaccines have low stability and require multiple injections in order to be effective. Poly lactic acid (PLA) has been approved as a biodegradable and biocompatible polymer for drug and vaccine delivery applications. The purpose of this study is to evaluate the antibody titer against the protective antigen recombinant protein (PA63) encapsulated by the mPEG-PLA double-block copolymers and to compare with the non-encapsulated PA63.Materials and Methods: To attain this purpose, to start, the desired protein was purified and confirmed and then PA63 was encapsulated with mPEG-PLA double-block copolymers using a water- oil- water solvent evaporation method. Produced nanoparticles was characterized in terms of morphological specifications using scanning electron microscopy, size and polydispersity index using dynamic light scattering and zeta potential using a zeta seizer. The synthesized nanoparticle antigenic content and also its antigen release profile was measured. In the following, the nanoparticles containing antigens (PA63-NPs), blank nanoparticles (mPEG-PLA- NPs), PA63 and adjuvant control were injected subcutaneously to mice and the IgG polyclonal antibody titr was measured by indirect ELISA. Finally to evaluate biocompatibility and toxicity, synthesized nanoparticles were investigated by cell culture testing.Results: The results of this study showed that the synthesized nanoparticles are of good quality. ELISA results showed that antibody production titr in mice receiving PA63-NPs was higher than those receiving the PA63 (P