Abstract
BackgroundThere has been a great interest in developing strategies for enhancing antigen delivery to the mucosal immune system as well as identifying mucosal active immunostimulating agents. To elevate the potential of O-2ʹ-Hydroxypropyl trimethyl ammonium chloride chitosan (O-2ʹ-HACC) as an adjuvant and mucosal immune delivery carrier for DNA vaccine, we prepared the O-2ʹ-HACC loaded with Newcastle disease virus (NDV) F gene plasmid DNA and C3d6 molecular adjuvant (O-2ʹ-HACC/pFDNA microparticles).ResultsThe O-2ʹ-HACC/pFDNA exhibited a regular spherical morphology with a particle size of 202.3 ± 0.52 nm, a zeta potential of 50.8 ± 8.21 mV, encapsulation efficiency of 90.74 ± 1.10%, and a loading capacity of 49.84 ± 1.20%. The plasmid DNA could be sustainably released from the O-2ʹ-HACC/pFDNA after an initial burst release. Intranasal vaccination of chickens immunized with O-2ʹ-HACC/pFDNA not only induced higher anti-NDV IgG and sIgA antibody titers but also significantly promoted lymphocyte proliferation and produced higher levels of IL-2, IL-4, IFN-γ, CD4+, and CD8 + T lymphocytes compared with the NDV commercial live attenuated vaccine. Intranasal delivery of the O-2ʹ-HACC/pFDNA enhanced humoral, cellular, and mucosal immune responses and protected chickens from the infection of highly virulent NDV compared with the intramuscular delivery.ConclusionsCollectively, our findings indicated that the O-2ʹ-HACC could be used as a vaccine adjuvant and delivery system for mucosal immunity and have an immense application promise.Graphic
Highlights
There has been a great interest in developing strategies for enhancing antigen delivery to the mucosal immune system as well as identifying mucosal active immunostimulating agents
The administration of DNA vaccine is given through an intramuscular injection (i.m.), and several studies have shown that DNA vaccines don’t effectively deliver antigen to antigen-presenting cells (APCs) after i.m
We focused on the side effect of the O-2’-HACC/pFDNA, and the results of in vitro and in vivo cytotoxicity showed that the O-2’HACC/pFDNA was safe within a certain concentration range
Summary
There has been a great interest in developing strategies for enhancing antigen delivery to the mucosal immune system as well as identifying mucosal active immunostimulating agents. The mucosal immune response can be improved by selecting the optimal immunization route, vaccine adjuvant, and delivery. The nasal mucosa is the first part to contact the inhaled antigen, nasal mucosal immunity can induce a stronger mucosal immune response and higher systemic immune responses in the distant mucosal tissues [3, 4], and intranasal vaccination is considered a more favorable mucosal immune route. Various strategies have been considered to enhance the mucosal immune response by using the suitable vaccine adjuvant, specific targeting of ligands, delivery system, and so on. Suitable vaccine adjuvant and delivery system in DNA vaccines can improve the immunogenicity, induce stronger immune responses, and reduce the dosage and production cost of vaccine in populations responding poorly to vaccination [10, 11]
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