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.
Highlights
The development of efficient and safe vaccines remains a major goal in globe public health
Nasal mucosa is an attractive site for DNA vaccines to evoke both systemic and mucosal immune response [6,7,8,9], due to its accessibility, lower enzyme distribution compared to the oral route and dense population of immune cells, often referred to as the nasal associated lymphoid tissue (NALT)
It is believed that development of vaccine against Streptococuus mutans (S. mutans) might be an effective strategy to prevent and control the occurrence of dental caries
Summary
The development of efficient and safe vaccines remains a major goal in globe public health. Considerable attention has been focused on the development of DNA vaccines as an effective immunogenic strategy to induce both humoral and cellular immune responses. DNA vaccines are considered to be inexpensive, stable, relatively safe compared to attenuated viral vaccines [1,2,3,4] and flexible to integrate genes encoding antigens and immunostimulatory sequences. Though intramuscular (i.m.) vaccination is still widely used, it usually failed in inducing local immunity at mucosal sites where tremendous infectious agents enter the body [5]. Nasal mucosa is an attractive site for DNA vaccines to evoke both systemic and mucosal immune response [6,7,8,9], due to its accessibility, lower enzyme distribution compared to the oral route and dense population of immune cells, often referred to as the nasal associated lymphoid tissue (NALT)
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