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Published on: May 19, 2020
Immunogenicity of meningococcal PorA formulations encapsulated in biodegradable microspheres
Carmen Arigita1, Joost van den Berg, Karin Wensink
1Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB, Utrecht, The Netherlands. w.jiskoot@pharm.uu.nl
Abstract:
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.
Insights
Researchers successfully microencapsulated Neisseria meningitidis outer membrane vesicles (OMVs) and liposomes containing pore protein A (PorA) into biodegradable microspheres. The encapsulated PorA formulations maintained their immunogenicity, showing promise for vaccine development.
Area of Science:
- Biotechnology
- Vaccine Development
- Materials Science
Background:
- Liposomes and outer membrane vesicles (OMVs) are key components in vaccine development.
- Neisserial pore protein A (PorA) is a critical antigen for meningococcal vaccines.
- Effective delivery systems are needed to enhance the immunogenicity and stability of vaccine antigens.
Purpose of the Study:
- To microencapsulate liposomes and OMV containing PorA into dextran- and mannan-based microspheres.
- To characterize the PorA formulations for size, structure, and antigen recovery.
- To evaluate the immunogenicity of the encapsulated PorA in a mouse model.
Main Methods:
- Aqueous two-phase system using polyethylene glycol and methacrylated dextran or mannan.
- Encapsulation of PorA-liposomes and OMV into microspheres.
- Characterization using size distribution analysis, antigen recovery assays, and in vitro release studies.
- Immunogenicity assessment in mice via subcutaneous immunization.
Main Results:
- High encapsulation efficiency (70-90%) for liposomes in dextran and mannan microspheres.
- Zero-order release kinetics observed for model liposomes between Days 5-10 in vitro.
- Preservation of trimeric PorA conformation and partial antigen recovery post-release.
- Maintained immunogenicity of encapsulated PorA-liposomes and OMV in mice.
Conclusions:
- Dextran- and mannan-based microspheres effectively encapsulate PorA-containing liposomes and OMV with high efficiency.
- The microencapsulation process preserves the structural integrity and immunogenicity of the PorA antigen.
- These findings support the potential of these biodegradable microspheres as a viable delivery system for meningococcal vaccines.
