Immunogenicity of meningococcal PorA formulations encapsulated in biodegradable microspheres

详细信息    查看全文

• 作者：Arigita ; Carmen ; van den Berg ; Joost ; Wensink ; Karin ; van Steenbergen ; Mies ; Hennink ; Wim E. ; et. al.
• 关键词：Neisseria meningitidis ; Vaccine ; PorA ; Liposomes ; Microspheres
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2004
• 出版时间：February, 2004
• 年：2004
• 卷：21
• 期：2-3
• 页码：131-141
• 全文大小：192 K

文摘

The purpose of our study was to investigate the possibility to microencapsulate liposomes and meningococcal outer membrane vesicles (OMV), both containing neisserial pore protein A (PorA), in biodegradable dextran- and mannan-based microspheres and to study the immunogenicity of the encapsulated PorA formulations. PorA-liposomes and OMV were encapsulated in dextran- or mannan-based microspheres by using an aqueous two-phase system consisting of a polyethylene glycol solution and a methacrylated dextran or mannan solution. The formulations were characterized for size distribution, PorA structure and antigen recovery after release. Calcein-containing model liposomes were used to establish the encapsulation efficiency and release profiles from both types of microspheres. The immunogenicity of the PorA-containing formulations was determined in mice after subcutaneous immunization. Liposomes were encapsulated in dextran and mannan microspheres with a high efficiency (70–90 % ). Calcein liposomes, after a 5-day lag period, exhibited apparent zero-order release kinetics from both types of microspheres between Days 5 and 10 of incubation in vitro. The total release was 80 and 100 % from mannan and dextran microspheres, respectively. The trimeric PorA conformation was preserved in the released liposomes and OMV and the antigen was partly recovered. The immunogenicity of PorA-liposomes and OMV encapsulated in dextran or mannan microspheres was preserved. In conclusion, PorA-liposomes and OMV could be encapsulated in dextran- and mannan-based microspheres with high efficiency. The immunogenicity of encapsulated antigen was preserved.