The Platform In Microencapsulation Technology For Viral Vaccine

The microencapsulated vaccine is a novel dosage form which can be controlled and delayed release to improve the vaccinal preparation and delivery by biodegradable materials and microencapsulation technology. It is expected to protect the antigens, to reduce the inoculation progresses and to enhance the immune effects. Therefore, the research of the microencapsulated viral vaccines is hopeful to overcome the shortages of traditional vaccines which are weak immunogenicitied, fast degraded and eliminated in vivo and low bioavailabilitied. It helps preventing and controlling transmitted diseases by virus.In this research, model of complete cellular, protein and DNA vaccine were from inactivated SARS coronavirus and hepatitis B vaccine, genetically engineered cells and SARS virus N gene eukaryotic expression plasmid, respectively. Through encapsulation methods, we altered the dosage forms. On the basis of study in the materials and preparation of encapculation, we constructed the elementary platform for the encapculation of viral vaccine and then evaluated systemic immune effects by animal inoculation.This work was divided into four parts:1. Matrix microsphere vaccine was made of (MPEG-PLGA) encapsulated inactivated SARS virus, a synthetic degradable polymer material, by membrane emulsification-drying method in liquid. The antigenicity of SARS virus was not destroyed in the encapsulation process because of the mild conditions of membrane emulsification-drying method in liquid.2. We studied the carrier materials and the technical parameters in the microencapsulated vaccine preparation, and by animals experiments by the commercial injection of hepatitis B vaccine, then tested the immune effect after injecting the microencapsulated vaccine. Results showed that the size of microcapsules in average is proportional to the aperture of SPG membrane and thecritical pressure. The vaccine entrapment ratio is high in the amphiphilic blocking copolymer PELG. The microencapsulated hepatitis B vaccine has great superiority in inducing mucosal and circulating antibodies (p<0.05).3. The microcapsules were transplanted into mouse abdomen with the genetically engineered cells transfected with antigen n gene of SARS virus as the core and natural material, sodium alginate and chitosan as membrane material. We found that the capsule membrane made of sodium alginate and chitosan had higher selective permeability. The encapsulated cells were good vectors in production and release of dissoluble genetically engineered antigens in vivo for improving the safety of gene immunity. 10-12 weeks after immune, there had no significant difference( p>0.05) between the microencapsulated cells and the recombinant plasmid in serum antibody titer induced. The combination of flt3 gene would raise the number of dendritic cells and Tc cells and then enhance mouse immunity.4. In the principle of self-assembling superrnolecular, viral DNA vaccine and synthetic cationic copolymer materials were assembled to nanoparticles or sub-microcapsules of shell-core structures in aqueous medium. These particles were transfected into cells subsequently. It was indicated that the DNA vaccine is more readily by cell uptake after assembled into nanoparticles. The genie transfection efficiency was enhanced and it is not affected from serum in the cell culture medium. Therefore, it is a prospective carrier for the DNA vaccine delivery in vivo.