A vaccine delivery system based on mannosylated chitosan microspheres (MCMs) was studied in vitro and in vivo. Bordetella bronchiseptica antigens containing dermonecrotoxin (BBD) were loaded in MCMs or chitosan microspheres (CMs). Fluorescence confocal microscopy indicated that BBD-loaded MCMs (BBD-MCMs) bound with mannose receptors on murine macrophages (RAW264.7 cells). In vitro experiments using macrophages demonstrated that BBD-MCMs had more effective immune-stimulating activity than BBD-loaded CMs (BBD-CMs). Mice intranasally immunized with BBD-MCMs showed significantly higher BBD-specific IgA antibody responses in saliva and serum than mice immunized with BBD-CMs (p<0.05). After challenge with B. bronchiseptica via the nasal cavity, groups treated with BBD-MCMs or BBD-CMs showed similar patterns with a high survival rate even though there was no significant difference between those groups. These results suggested that mannose moieties in the MCMs enhanced immune-stimulating activities through mucosal delivery due to a specific interaction between mannose groups in the MCMs and mannose receptors on the macrophages.
"Non-viral methods of gene delivery, including cationic polymers and lipids that can form polyplexes with DNA vaccines are another promising approach, since DNA polyplexes are efficiently protected from enzymatic degradation and exhibit increased cell transfection efficiency  . Likewise, cationic polymer carriers containing mannose moieties have been reported to mediate targeted DNA delivery to professional antigen presenting cells (APCs), including macrophages and dendritic cells  . However, cationic polymer-based DNA vaccines still require a trained healthcare professional to perform the injection with a hyperdermic syringe. "
[Show abstract][Hide abstract] ABSTRACT: Microneedle (MN)-based DNA vaccines have many advantages over conventional vaccines administered by hypodermic needles. However, an efficient strategy for delivering DNA vaccines to intradermal cells has not yet been established. Here, we report a new approach for delivering polyplex-based DNA vaccines using MN arrays coated with a pH-responsive polyelectrolyte multilayer assembly (PMA). This approach enabled rapid release of polyplex upon application to the skin. In addition to the polyplex-releasing MNs, we attempted to further maximize the vaccination by developing a polymeric carrier that targeted resident antigen presenting cells (APCs) rich in the intradermal area, as well as a DNA vaccine encoding a secretable fusion protein containing amyloid beta monomer (Aβ1-42), an antigenic determinant. The resulting vaccination system was able to successfully induce a robust humoral immune response compared to conventional subcutaneous injection with hypodermal needles. In addition, antigen challenge after immunization elicited an immediate and strong recall immune response due to immunogenic memory. These results suggest the potential utility of MN-based polyplex delivery systems for enhanced DNA vaccination.
"In a recent study, nine ILs (differing by their ion type or chain length on the cation) have been screened for the same synthesis whilst 1-butyl- 1-methylpyrrolidinium trifluoromethanesulfonate [Bmpyrr][TFO] was highlighted as the best in terms of yield and reaction rate . These studies focus on mannose esters because mannose vaccine or drug carrier can be interesting for increasing immunogenicity   and tumor targeting . As for the choice of the acyl moiety, molecules based on myristic acid are used to modify proteins by myristoylation for protein-membrane binding and protein-protein interactions improvement  . "
[Show abstract][Hide abstract] ABSTRACT: The purpose of the present study is to find the conditions allowing to reach the highest 24 h-yield (24 h-η) for the synthesis of mannosyl myristate catalyzed by the immobilized lipase B from Candida antarctica (Novozym® 435) in the ionic liquid (IL) [Bmpyrr][TFO] (1-butyl-1-methylpyrrolidinium trifluoromethanesulfonate). A full factorial design (FFD) was used in order to study the influence of three variables (temperature, mannose/vinyl myristate ratio and total substrate quantity) on the 24 h-η. This design led to a model based on a second order polynomial response function. The resulting predicted contour plots have shown that the highest 24 h-η should be obtained with high temperatures, low sugar/vinyl ester molar ratio and intermediate total substrate quantities (mmol). The model has been successfully verified and experimentally confirmed at the optimal conditions of 80 °C, substrate molar ratio of 1/10 and total substrate quantity of 0.26 mmol leading to the highest predicted 24 h-η of 72.2%.
Process Biochemistry 08/2013; 48(12). DOI:10.1016/j.procbio.2013.08.023 · 2.52 Impact Factor
"Thus, the problem of inefficient delivery for the plasmid vector must be addressed before achieving a better outcome for the DNA vaccine. It is well known that APCs, such as dendritic cells (DCs), express a large amount of mannose receptor on the surface.14 To enhance the specificity of drug delivery, a large number of research papers have explored different mannosylated drug delivery systems, such as mannosylated chitosan,14 mannosylated liposome,15 and mannosylated polyethyleneimine 25k (PEI 25k). "
[Show abstract][Hide abstract] ABSTRACT: The heterologous deoxyribonucleic acid (DNA) prime-adenovirus (AdV) boost vaccination approach has been widely applied as a promising strategy against human immunodeficiency virus (HIV)-1. However, the problem of inefficient delivery and lack of specificity of DNA vaccine remains a major issue. In this paper, to improve the transfection of DNA vaccine and realize dendritic cell targeting, we used mannosylated polyethyleneimine (man-PEI) as a DNA vector carrier.
The DNA plasmid encoding antigen HIV gag fragment was constructed by polymerase chain reaction. Then the DNA plasmid was complexed with man-PEI. The in vitro transfection efficiency of man-PEI/DNA was analyzed on DC 2.4 cells. Mice were primed with 25 μg pVAX1-HIV gag plasmid complexed with man-PEI, 100 μg naked pVAX1-HIV gag plasmid, or empty pVAX1 vector and boosted by AdV encoding the same antigen. The antibody titer, CD4(+) and CD8(+) T-cell response, as well as interferon-γ and interleukin-4 levels in serum and in splenocytes culture were analyzed using flow cytometry or enzyme-linked immunosorbent assay to evaluate the immune response. To test a long-term effect of the vaccination regimen, CD8(+) memory T-cell was also detected by flow cytometry.
The pVAX1-HIV gag was constructed successfully. The in vitro transfection efficiency in dendritic cells was significantly higher than naked DNA plasmid. Compared with 100 μg naked DNA/AdV group, the immunoglobulin G2a antibody titer, T-cell response percentage, and cytokine production level induced by man-PEI/DNA/AdV group were significantly higher at a lower DNA dose. Also, the man-PEI/DNA could stimulate a memory CD8(+) T-cell response.
Owing to the adjuvant effect of man-PEI, the man-PEI/pVAX1-HIV gag priming plus AdV boosting strategy proved to be a potent vaccine candidate against HIV, which could induce a stronger immune response with a lower DNA dose.
International Journal of Nanomedicine 05/2013; 8:1843-1854. DOI:10.2147/IJN.S43827 · 4.38 Impact Factor
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