The highly contagious Newcastle disease virus (NDV) continues to threaten poultry all over the world. The NDV
DNA vaccine is a promising
solution to the current
Newcastle disease (ND) challenges, and thus an efficient delivery system should be developed to facilitate the efficacy of
DNA vaccines. In this study, we developed
a DNA vaccine delivery system consisting of a triblock copolymer of
poly(lactide co-glycolide acid) and
polyethylene glycol (PLGA-
PEG-PLGA)
hydrogel in which the recombinant NDV
hemagglutinin-
neuraminidase (HN) plasmid was encapsulated. Its characteristics, security, immune responses, and efficacy against highly virulent NDV were detected. The results showed that the plasmids were gradually released in a sustained manner from the
hydrogel, which improved the
biological stability of the plasmids and demonstrated a high biocompatibility. The plasmids, when they were incorporated into the
hydrogel delivery system, enhanced immune activation and provided 100% protection against the highly virulent NDV strain. Furthermore, we proved that this NDV
DNA hydrogel vaccine could improve the lymphocyte proliferation and increase the immunological
cytokine production via the PI3K/Akt pathway. These results indicate that the PLGA-
PEG-PLGA thermosensitive
hydrogel could be a promising delivery system for the NDV
DNA vaccine in order to achieve a sustained supply of plasmids and induce potent immune responses.