Study On Suspension Stability And Immune Mechanism Of Self-assembled Aluminum Adjuvant

Aluminum-based adjuvants(Alum)are widely used in pharmaceutical preparations due to their ability to induce humoral immunity and good safety.Aluminum-based vaccine adjuvants are usually prepared as suspensions,which are prone to spontaneous aggregation,stratification and sedimentation.When the antigen was adsorbed to the surface of the aluminum-based adjuvant in the vaccine formulation,the adjuvant-antigen complex is exposed to the action of interfacial stress.The phenomenon of stratification and sedimentation was more obvious,which further led to impaired immune stimulation and reduced the vaccine effect.Aluminum-based adjuvants are as an inorganic material,their suspension stability are affected by many factors,including particle size,surface potential and rheology.The addition of excipients and surface modification methods can increase electrostatic repulsion and steric stabilization.These strategies have been shown to stabilize vaccine formulations and improve suspension stability.However,these methods are too complicated and cumbersome,and there will be disadvantages of changing the properties of adjuvants.At present,few reports have been reported to optimize the suspension stability of vaccine by adjust the inherent properties of aluminum-based adjuvants to avoid aggregation.In this study,a library of assemble-self rice-like aluminum hydroxide nanoadjuvants(NRs)with different aspect ratios was synthesized by hydrothermal method.In the synthetic process,the engineered aggregations NRs formd by controlling the atomic interface coupling,which reduce their surface free energy.Hence,the suspension stability NRs of was improved.Fourthermore,different antigen models were selected to refine vaccine formulations and determined the ability of NRs optimize vaccine suspension stability.After adsorption of hepatitis B surface antigen,human papillomavirus(HPV)VLPs and bovine serum albumin(BSA),the NRs-antigen complex still showed better suspension stability,less precipitation and longer stabilization time.In a mouse model,Hepatitis B antigen(HBs Ag)VLPs were used for immunization.The immunization results proved that NRs had a good adjuvant effect,and NRs with high aspect ratio could induce stronger humoral immune responses due to their better endocytosis effect.This study improves suspension stability by controlling the inherent properties of aluminum oxyhydroxide adjuvants,which provides insights into the design of engineered adjuvants with superior suspension stability and further ensures improved vaccine immunogenicity.