Reaserch On Stability Of HEV Vaccine When Antigen Is Adsorbed By Aluminum-hydroxide Adjuvant

To improve the stability of HEV vaccine, phosphate and multihydroxy-compound need to be added which can control aging behavior of adjuvant. This paper, from adsorption percentage of antigen and immunogenicity, explores method that can improve stability of HEV vaccine. Antibody titer of serum is used as key criterion for evaluation of vaccine stability.Effects of volume ratio、temperature and time when aluminum-hydroxide adjuvant adsorb HEV antigen、kind of phosphate saline which is used to pretreat aluminum-hydroxide adjuvant and pH of vaccine to adsorption percentage of antigen are explored. On this basis, partial forces of adsorption are clarified. Variation of antigen’s adsorption capacity (Γm) are explored, by changing ionic strength (sodium chloride) and concentration of hydrophobic substance (ethylene glycol) in vaccine. Conclusion that electrostatic attractive force and hydrophobic force affect adsorption is confirmed by regular change ofΓm and the two substances contents. Effect of adsorption force on Fm is used as guide, adjuvant with proper amount additives which can inhibit aging is used to prepare experimental vaccine. The experimental vaccine is desorbed with sheep lymph fluid, adsorption percentage of antigen changes correspondingly as content of additives changes. The result suggests that additives change strength of adsorption, and may improve immunogenicity.Outcome of experiment in vivo show that patches of adjuvant lead to inconsistency of immunogenicity. To improve vaccine stability and minish differences of vaccine quality caused by patch of adjuvant, orthogonal test L18(37) is designed. The result shows that concentration of phosphate affects antibody titer significantly, and more phosphate, higher antibody titer. Because that in orthogonal test is lower, concentration of phosphate is increased continuously to investigate change of antibody titer. When phosphate concentration is above 4 mmol/L, antibody titer reached steady state. When phosphate is at 6 mmol/L, experiment of phosphate kind and vaccine pH is performed. Antibody titer level of vaccine with NaH2PO4 is higher than vaccine with PB, and it is not affected by vaccine pH. In the end, ingredients which can stabilize vaccine and may get rid of adjuvant patch are fixed.