Study On The Biological Characteristics Of Mesoporous Silica As A Vaccine Adjuvant

Mesoporous silica nanomaterials?MSs?have excellent physicochemical properties,such as large specific surface area,high pore volume,easy modification,simple synthesis process,easily tunable parameters of reaction.However,in the past few decades,MSNs have been increasingly used in catalysis,biosensing,energy storage,small molecule/macromolecule drug delivery,and biomolecule immobilization of proteins/peptides.In recent years,the inorganic MSNs have been used as a promising alternative to conventional emulsions or liposomes in the field of immunization have attracted ever-increasing attention.The main work of this thesis is to use type-O foot-and-mouth disease virus-like particles?VLPs?as antigens,guinea pigs as animal models,and silica nanomaterials with three different morphological structures as adjuvants to load VLPs to immunize guinea pigs.The biocompatibility of the three mesoporous silica was investigated by cytotoxicity experiments,hemolysis assay,endocytosis experiments,histopathological analysis and degradation experiments in vitro.The specific antibodies and neutralizing antibodies were detected,the protection rate after challenge was also calculated.From the results of antibody level and the protection rate after challenge,it was found that all three mesoporous silica have adjuvant effects.The research work of this thesis provides an experimental basis for the application of mesoporous silica nanomaterials in the field of immunity.The main work of this thesis is as follows:1.Synthesis and characterization of mesoporous silica nanomaterials.Hollow mesoporous silica nanoparticles?HMSNs?were prepared by using TEOS as silicon source,CTAB as surfactant and PS microsphere as template in ethanol-water phase;dendritic mesoporous silica nanoparticles?MSNs?prepared by using TEOS as silicon source,CTAC as surfactant and TEA as catalyst in chlorobenzene-water phase;nuclear cone-shaped mesoporous silica nanoparticles?DMSNs?were prepared from solid silica as substrate,TEOS as silicon source,CTAC as surfactant and TEA as catalyst in chlorobenzene-water phase,and the effects of substrate?SN100?,reaction conditions?temperature,rotation speed and reaction time?and reagents?TEOS,CTAC,H₂O,chlorobenzene and TEA?during the synthesis of DMSNs were investigated.The pthysicochemical characterizations of HMSNs,MSNs and DMSNs were performed by TEM,SEM,BET,BJH and FTIR.2.Biocompatibility of mesoporous silica nanoparticles.The biocompatibility of mesoporous silica nanoparticles was investigated by hemolysis assay,cytotoxicity experiment and degradation experiments in vitro.3.Guinea pig immunization and challenge experiments.The guinea pigs were immunized with three different types of mesoporous silica nanoparticles loaded with VLPs,and the adjuvant effects of the three mesoporous silica materials were evaluated by specific antibody,neutralizing antibody levels and challenge protection rate.