Development of PLGA-PEG-PLGA Hydrogel Delivery System for Enhanced Immunoreaction and Efficacy of Newcastle Disease Virus DNA Vaccine

Abstract

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.

Nanovaccine Delivery Approaches and Advanced Delivery Systems for the Prevention of Viral Infections: From Development to Clinical Application

“…Thermo-responsive polymers that form hydrogels at body temperature also proved to be useful for formulation of vaccine depot gels. An example of this is the thermosensitive triblock copolymer hydrogel comprised of (PLGA-PEG-PLGA), which was utilised by Gao et al to develop a DNA vaccine delivery system for the encapsulation of the recombinant hemagglutinin-neuraminidase plasmid of the avian Newcastle disease virus (NDV) [261]. This triblock copolymer undergoes postinjection hydrogelation triggered by host body temperature, leading to sustained release of the plasmid from the hydrogel matrix.…”

Towards Improved Use of Vaccination in the Control of Infectious Bronchitis and Newcastle Disease in Poultry: Understanding the Immunological Mechanisms

“…Generally, most of the vaccines reported (Table 2) are live attenuated vaccines and/or inactivated vaccines. Live attenuated vaccines are faced with certain safety concerns; the possibility of reversion to virulence, the need for biocontainment during production and cold-chain requirements [147]. Inactivated vaccines, on the other hand, are faced with poor immunogenicity and if not completely inactivated, may cause disease [147].…”

“…Live attenuated vaccines are faced with certain safety concerns; the possibility of reversion to virulence, the need for biocontainment during production and cold-chain requirements [147]. Inactivated vaccines, on the other hand, are faced with poor immunogenicity and if not completely inactivated, may cause disease [147]. Therefore, the need for improvement in ND vaccine development and vaccination cannot be overemphasized.…”

“…DNA vaccines have emerged as a novel strategy for vaccination against ND infection. It is thought to be safe, genetically stable, convenient, and immunogenic [147]. However, following the challenges of DNA vaccines including low bioavailability and degradation before reaching the antigen-presenting cells (APCs), Gao and co, developed a DNA vaccine delivery system made up of copolymer of poly (lactide-co-glycolide acid) and polyethylene glycol (PLGA-PEG-PLGA) hydrogel, encapsulating the recombinant NDV hemagglutininneuraminidase (HN) plasmid.…”

“…They achieved gradual and sustained release of the plasmid from the hydrogel, improving the biological activity. According to the group, the NDV DNA hydrogel vaccine not only provided a 100% protection, but it also enhanced both humoral and cellular immunity against a highly virulent NDV (F48E9 strain) [147]. Similarly, earlier studies by some other groups demonstrated the effectiveness of N-2-hydroxypropyltrimethyl ammonium chloride chitosan (N-2-HACC) and N, O-carboxymethyl chitosan (CMC) (N-2-HACC-CMC) and chitosan (CS)-coated poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) as an immune delivery carrier for DNA vaccines [100,163,164].…”