Nanoparticle vaccines are an emerging platform for co-delivering immunostimulatory adjuvants and antigens. These platforms aim to increase the efficiency of uptake by antigen-presenting cells and to promote immune activation. They offer a promising strategy to improve vaccine efficiency and efficacy while allowing spatial control of antigen and adjuvant delivery to the same cell. The purpose of this study was to design, characterize, and evaluate a polycationic PEI/HA-CpG (PHC) nanoparticle vaccine consisting of polyethyleneimine, Influenza B hemagglutinin and nucleoprotein, and CpG as an adjuvant, for innate immune activation. PHC nanoparticles were synthesized and characterized based on particle size, polydispersity index, and surface charge. Their immunological activity was evaluated by stimulating JAWS II, RAW 264.7, and bone-marrow derived dendritic cells and measuring inflammatory cytokine production compared with unstimulated controls and monophosphoryl lipid A as a positive control. In addition, the physicochemical stability of the nanoparticle platform was evaluated over a one-month period by monitoring the changes in particle size, polydispersity index, and surface charge. Stimulation of these cells with the PHC nanoparticle resulted in increased inflammatory cytokine production compared with negative controls. These findings indicate that the PHC nanoparticle platform can stimulate innate immune responses in antigen-presenting cells and provide support for further evaluation of the B/Brisbane-BNP PEI-HA/CpG nanoparticle formulation as a potential influenza B vaccine platform.