Enhancing Mucosal Immune Response of Newcastle Disease Virus DNA Vaccine Using N-2-Hydroxypropyl Trimethylammonium Chloride Chitosan and N,O-Carboxymethyl Chitosan Nanoparticles as Delivery Carrier

Abstract

Because mucosal sites are the entry ports of pathogens, immunization via mucosal routes can extremely enhance the immunity. To elevate the potential of N-2-hydroxypropyl trimethylammonium chloride chitosan (N-2-HACC) and N,O-carboxymethyl chitosan (CMC) nanoparticles as a mucosal immune delivery carrier for DNA vaccines, we prepared the NDV F gene plasmid DNA with C3d6 molecular adjuvant (pVAX I-F(o)-C3d6) encapsulated in the N-2-HACC-CMC nanoparticles (N-2-HACC-CMC/pFDNA-C3d6 NPs). The N-2-HACC-CMC/pFDNA-C3d6 NPs had regular spherical morphology and low toxicity with a mean diameter of 309.7 ± 6.52 nm, zeta potential of 49.9 ± 4.93 mV, encapsulation efficiency of 92.27 ± 1.48%, and loading capacity of 50.75 ± 1.35%. The N-2-HACC-CMC had high stability and safety. The pVAX I-F(o)-C3d6 could be sustainably released from the N-2-HACC-CMC/pFDNA-C3d6 NPs after an initial burst release. Immunization intranasally of chickens with N-2-HACC-CMC/pFDNA-C3d6 NPs not only produced higher anti-NDV IgG and sIgA antibody than chickens in other groups did, but also significantly stimulated lymphocyte proliferation and triggered higher the IL-2, IL-4, and IFN-γ levels. These findings indicated that the N-2-HACC-CMC could be used as an efficient delivery carrier for the mucosal immunity of Newcastle disease virus DNA vaccine. The work laid a basis for the quaternized chitosan nanoparticles as efficient mucosal immunity delivery carrier for DNA vaccines and had immense application promise and potential for vaccines and drugs.

Applications of polymer-based nanoparticles in vaccine field

“…Our group developed the plasmid DNA of NDV F gene encapsulated in the N-2-HACC/CMCS nanoparticles, and found that intranasally immunized chickens with the nanoparticles produced higher anti-NDV IgG and sIgA antibody than the chickens in other groups did. They also had significantly stimulated lymphocyte proliferation and higher levels of induced IL-2, IL-4 and IFN-levels, which demonstrated that the nanoparticles could serve as efficient DNA delivery systems and vaccine adjuvants for stimulating humoral, cellular, and mucosal immune [58].…”

Diagnostic and Vaccination Approaches for Newcastle Disease Virus in Poultry: The Current and Emerging Perspectives

“…More so, when administered without any delivery vehicle, they are easily degraded by the nucleases before they reach their final destination. Nonetheless, the use of adjuvants and delivery vehicle may overcome some of these limitations [ 142 , 143 ].…”

Construction of a novelDNAvaccine candidate targeting F gene of genotypeVIINewcastle disease virus and chickenIL‐18 delivered bySalmonella

“…) and DNA vaccine (Zhao et al . ) have been studied. In particular, the DNA vaccine, named ‘the third‐generation vaccine’, has attracted increased interest recently because of its easy manipulation and stability for transportation (Heppell and Davis ).…”

“…Although vaccination is the best way to prevent ND, vaccine failure in providing protection against genotype VII ND has been reported (Ji et al 2018). In addition to the traditional inactivated vaccine, vaccine candidates such as the reverse genetics vaccine (Kim and Samal 2018), subunit vaccine (Kang et al 2016) and DNA vaccine (Zhao et al 2018) have been studied. In particular, the DNA vaccine, named 'the third-generation vaccine', has attracted increased interest recently because of its easy manipulation and stability for transportation (Heppell and Davis 2000).…”