Preparation Of Aluminum-based Adjuvant By Using CSTR And Analysis Of Their Immunological Potentials

In the prevention of influenza disease,vaccine as a powerful tool can make ourselves produce antibodies to fight the influenza virus.The adjuvants in vaccines can enhance the immune response due to the storage effect.Aluminum salts as adjuvants are the most extensively formulated in vaccines because of more security and low-cost.As an immunopotentiator,it was demonstrated that adjuvanticity of aluminum oxyhydroxide(Al OOH)nanoparticles is correlative to their morphology,crystallinity and surface hydroxyl contents.The strict control of physiochemical properties of aluminum oxyhydroxide adjuvant is important to exert the adjuvant effect and ensure the quality of vaccines.To date,there are many methods using intermittent reactor to fabricate aluminum oxyhydroxide nanoparticles with controllable physiochemical properties.However,the traditional dripping process can’t be produced continuously and the limitation of higher energy consumption hinders further industrial amplification process and can’t meet the needs of industrialization.In this study,a continuous stirring tank reactor(CSTR)was used in the synthesis process of aluminum oxyhydroxide nanoparticles.Additionally,two approaches,including elevation of p H during reaction and extension of reaction time were tested to tun the physiochemical properties of synthetic nanoparticles.By the way of continuous and constant reactant conditions,we synthesized a library of aluminum oxyhydroxide nanoparticles with high reproducibility and uniformity.We demonstrate that morphology,aspect ratio,crystallinity of the final nanoparticles can be accurately controlled by adjusting reaction p H and time.Aluminum oxyhydroxide nanorods generated in acidic environment show good stability and protein adsorption capacity.Moreover,compared with commercial Alum,aluminum oxyhydroxide nanorods Rod 1 elicited perdurable humoral immunity in wild type mice,indicating excellent immunopotentiation capabilities.However,by experimental characterization and comparison,we demonstrate that aluminum oxyhydroxide nanosheets synthesized in basic environment are not stable during aging and produce the bayerite.So nanosheets are not suitable for protein adsorption experiments.We found that Rod 1 induced a more persistent immune response in vivo.The optimization of the synthesis process not only regulates the physicochemical properties of products precisely,but also maintains that the synthesis conditions are constant and continuous,which facilitates further process scale-up.The theoretical basis for the preparation process of aluminum adjuvant was laid.