Mannosylated and lipid A-incorporating cationic liposomes constituting microneedle arrays as an effective oral mucosal HBV vaccine applicable in the controlled temperature chain

作者：Wang, Ting^*; Zhen, Yuanyuan; Ma, Xiaoyu; Wei, Biao; Li, Shuqin; Wang, Ning

来源：Colloids and Surfaces B: Biointerfaces , 2015, 126: 520-530.

DOI：10.1016/j.colsurfb.2015.01.005

• Liposomes
• Microneedles
• Mucosal immunization
• Freeze-drying
• C-type lectin receptor

To develop an effective, convenient and stable mucosal vaccine against hepatitis B virus (HBV), the mannose-PEG-cholesterol/lipid A-liposomes (MLLs) loaded with HBsAg were prepared by the procedure of emulsification-lyophilization and, subsequently, filled into the microholes of microneedle array reverse molds and dried to form the proHBsAg-MLLs microneedle arrays (proHMAs). The proHMAs were stable even at 40 degrees C for up to 3 days and hard enough to pierce porcine skin but, upon rehydration, rapidly dissolved recovering the HBsAg-MLLs without obvious changes in size and antigen association efficiency. Notably, immunization of mice only once with the proHMAs at oral mucosa induced robust systemic and widespread mucosal immunoresponses, as evidenced by the high levels of HBsAg-specific IgG in the sera and IgA in the salivary, intestinal and vaginal secretions. In addition, a strong cellular immunity against HBV had been established through a mixed Th1/Th2 response, as confirmed by a significant increase in CD8( ) T cells as well as the enhanced levels of IgG2a and IFN-gamma in the treated mice. Thus, the pro HMAs can be conveniently vaccinated via oral mucosal route to set up a multiple immune defense against HBV invasion and, in addition, may be a stable HBV vaccine applicable in the controlled temperature chain for wide distribution.

• 出版日期2015-2-1
• 单位安徽医科大学; 合肥工业大学