Protection against tuberculosis achieved by dissolving microneedle patches loaded with live Mycobacterium paragordonae in a BCG prime-boost strategy.

Introduction: Skin vaccination using dissolving microneedle patch (MNP) technology for transdermal delivery is a promising vaccine delivery strategy to overcome the limitations of the existing vaccine administration strategies using syringes. To improve the traditional microneedle mold fabrication technique, we introduced droplet extension (DEN) to reduce drug loss. Tuberculosis remains a major public health problem worldwide, and BCG revaccination had failed to increase the protective efficacy against tuberculosis. We developed an MNP with live Mycobacterium paragordonae (Mpg) (Mpg-MNP) as a candidate of tuberculosis booster vaccine in a heterologous prime-boost strategy to increase the BCG vaccine efficacy. Materials and methods: The MNPs were fabricated by the DEN method on a polyvinyl alcohol mask film and hydrocolloid-adhesive sheet with microneedles composed of a mixture of mycobacteria and hyaluronic acid. We assessed the transdermal delivery efficiency by comparing the activation of the dermal immune system with that of subcutaneous injection. A BCG prime Mpg-MNP boost regimen was administered to a mouse model to evaluate the protective efficacy against M. tuberculosis. Results: We demonstrated the successful transdermal delivery achieved by Mpg-MNP compared with that observed with BCG-MNP or subcutaneous vaccination via an increased abundance of MHCII-expressing Langerin+ cells within the dermis that could migrate into draining lymph nodes to induce T-cell activation. In a BCG prime-boost regimen, Mpg-MNP was more protective than BCG-only immunization or BCG-MNP boost, resulting in a lower bacterial burden in the lungs of mice infected with virulent M. tuberculosis. Mpg-MNP-boosted mice showed higher serum levels of IgG than BCG-MNP-boosted mice. Furthermore, Ag85B-specific T-cells were activated after BCG priming and Mpg-MNP boost, indicating increased production of Th1-related cytokines in response to M. tuberculosis challenge, which is correlated with enhanced protective efficacy. Discussion: The MNP fabricated by the DEN method maintained the viability of Mpg and achieved effective release in the dermis. Our data demonstrate a potential application of Mpg-MNP as a booster vaccine to enhance the efficacy of BCG vaccination against M. tuberculosis. This study produced the first MNP loaded with nontuberculous mycobacteria (NTM) to be used as a heterologous booster vaccine with verified protective efficacy against M. tuberculosis.

Effect of spark plasma sintering on plasma electrolytic oxidation coatings on gas-atomized Mg-Zn-Y alloy containing nano-sized powders.

Mg-1.0wt%Zn-2.0wt%Y alloy powders were produced by gas atomization, and subsequently sintered by spark plasma sintering (SPS). The SPSed Mg-1.0wt%Zn-2.0wt%Y alloy, which showed a microstructure of well-bonded grains containing nano-sized powders of approximately 100 nm in diameter, was coated by a plasma electrolytic oxidation (PEO) method. Microstructure, mechanical properties and corrosion properties of PEO coatings were investigated and compared to those of normally sintered Mg-1.0wt%Zn-2.0wt%Y and cast Mg-1.0wt%Zn alloys. All coatings consisted of MgO and Mg2SiO4. The micro-hardness and friction coefficient of coatings on the SPSed Mg-1.0wt%Zn-2.0wt%Y alloy were higher than those on normally sintered Mg-1.0wt%Zn-2.0wt%Y and cast Mg-l.0wt%Zn alloys. However, the corrosion resistance in 3.5% NaCl solution for the SPSed Mg-1.0wt%Zn-2.0wt%Y alloy was between that for normally sintered Mg-1.0wt%Zn-2.0wt%Y alloy and cast Mg-1.0wt%Zn alloy.