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.
Highlights
Newcastle disease (ND) is a highly contagious viral disease in poultry which leads to high mortality and huge economic losses in the poultry industry
The phase-transition temperature (Tm), gelation time (Gt), and viscosity of the aqueous solutions of the PLGA-polyethylene glycol (PEG)-PLGA copolymer at various concentrations were determined to elect the optimal concentration for the copolymer-based hydrogel
The DNA vaccine presents several advantages over conventional vaccines, such as its security and ability to be a multivalent vaccine. It can induce both humoral and cellular immunity, which are more effective in preventing diseases such as viral infections that rely on cellular immune clearance [8]
Summary
Newcastle disease (ND) is a highly contagious viral disease in poultry which leads to high mortality and huge economic losses in the poultry industry. The Newcastle disease virus (NDV) is an avian paramyxovirus type 1 virus belonging to the genus Avulavirus within the family. The genome of NDV is a non-segmented, negative-sense, single-stranded RNA genome of 15,186 to 15,198 nucleotides in length, encoding six structural proteins: nuclear protein (N), phosphoprotein (P), large polymerase protein (L), matrix protein (M), hemagglutinin-neuraminidase (HN), and fusion protein (F). Among these proteins, the HN protein, as the main protective antigen on the surface of NDV, has good immunogenicity [3,4]. The inactivated vaccines generally have poor immunogenicity and may Molecules 2020, 25, 2505; doi:10.3390/molecules25112505 www.mdpi.com/journal/molecules
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