title: Enhanced nasal mucosal delivery and immunogenicity of anti-caries DNA vaccine through incorporation of anionic liposomes in chitosan/DNA complexes.
abstract: The design of optimized nanoparticles offers a promising strategy to enable DNA vaccines to cross various physiological barriers for eliciting a specific and protective mucosal immunity via intranasal administration. Here, we reported a new designed nanoparticle system through incorporating anionic liposomes (AL) into chitosan/DNA (CS/DNA) complexes. With enhanced cellular uptake, the constructed AL/CS/DNA nanoparticles can deliver the anti-caries DNA vaccine pGJA-P/VAX into nasal mucosa. TEM results showed the AL/CS/DNA had a spherical structure. High DNA loading ability and effective DNA protection against nuclease were proved by gel electrophoresis. The surface charge of the AL/CS/DNA depended strongly on pH environment, enabling the intracellular release of loaded DNA via a pH-mediated manner. In comparison to the traditional CS/DNA system, our new design rendered a higher transfection efficiency and longer residence time of the AL/CS/DNA at nasal mucosal surface. These outstanding features enable the AL/CS/DNA to induce a significantly (p<0.01) higher level of secretory IgA (SIgA) than the CS/DNA in animal study, and a longer-term mucosal immunity. On the other hand, the AL/CS/DNA exhibited minimal cytotoxicity. These results suggest that the developed nanoparticles offer a potential platform for DNA vaccine packaging and delivery for more efficient elicitation of mucosal immunity.
authors: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, PR China.
authors: Liulin
authors: L
authors: Chen
authors: Junming
authors: J
authors: Zhu
authors: Yuhong
authors: Y
authors: Li
authors: Jie
authors: J
authors: Lu
authors: Li
authors: L
authors: Gao
authors: Huibi
authors: H
authors: Xu
authors: Mingwen
authors: M
authors: Fan
authors: Xiangliang
authors: X
authors: Yang
mesh_terms: D000281:Administration, Intranasal; D000327:Adsorption; D000818:Animals; D000838:Anions; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D018938:Caco-2 Cells; D002470:Cell Survival; D048271:Chitosan / Q000737:chemistry*; D004269:DNA, Bacterial / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D003731:Dental Caries / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007110:Immunity, Active; D018928:Immunity, Mucosal; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009077:Mucins / Q000737:chemistry; D053769:Nanocapsules / Q000737:chemistry; D009297:Nasal Mucosa / Q000276:immunology*; D010316:Particle Size; D051381:Rats; D012463:Saliva / Q000378:metabolism; D013295:Streptococcus mutans / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology
chemical_list: D000838:Anions; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D004269:DNA, Bacterial; D008081:Liposomes; D009077:Mucins; D053769:Nanocapsules; D019444:Vaccines, DNA; D048271:Chitosan
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