| Vaccination to protect against human infectious diseases may be enhanced by using adjuvants that can selectively stimulate immunoregulatory responses. Aluminum salts have been used for near 80 years as adjuvants in vaccines. Alum adjuvants in commercial vaccines have been characterized as aluminum oxyhydroxide (A1OOH, a crystalline aluminum oxyhydroxide, commonly referred to as aluminum hydroxide) and aluminum hydroxyphosphate (Al(OH)x(PO4)y, commonly referred to as aluminum phosphate). Aluminum hydroxide has been demonstrated to have a more potent adjuvant effect than aluminum phosphate which may be due to its higher adsorption capacity and better adsorption of certain antigens at neutral pH, which is positively charged at physiological pH=7.4 [isoelectric point (iep) = 11.4], which is also the only certificated adjuvant for human vaccine by FDA of USA. Although aluminum hydroxide adjuvants have been used for a long time, surprisingly little is known about the mechanisms by which they enhance the immune response. The two most commonly cited mechanisms are "formation of an antigen depot" and "immunostimulation". Adsorption may ensure a high-localized concentration of antigen for a period of time that is sufficient to allow antigen uptake and activation of dendritic cells.Adsorption of antigens on aluminum hydroxide adjuvants depends upon physical and chemical characteristics of antigen and other conditions of adsorption include pH, temperature, size of the gel particles and ionic strength of the reaction mixture. These conditions are often overlooked and a poorly formulated aluminum hydroxide adjuvant preparation does not give optimal adjuvanticity. Size of gel particles affects the surface area of gel available for adsorption: small particles have more surface area than large particles. For example, amount of diphtheria toxoid adsorbed on to aluminum hydroxide gels was inversely proportional to the gel particle size.In our study, hepatitis B surface antigen (HBsAg) was as model antigen of alum adjuvant, main in view of these: HBsAg is a complex macromolecular aggregate composedof protein, carbohydrates, and lipids. It has a molecular weight of 3500 kDa. Phospholipids account for almost 70% of the lipids. The adsorption of HBsAg by aluminum hydroxide adjuvant is not by electrostatic attraction and hydrophobic interactions but by phosphate groups of HBsAg adsorbing strongly to hydroxylated aluminum surfaces by ligand exchange. The absorbtion is less changing and elution in viro and in vitro. When alum adjuvant becomes nanometer particles to adsorb HBsAg, sharp decreasing surface area would be the main influence, it has excellent behavior that surface responses is higher surface active center is the more and adsorption ability is stronger, which affects absorbtion and absorbs more antigen.Nanoparticles are closed relationship between the nanoparticle and the organism. For the nanoparticle adjuvant, it is a targeted cellular uptake by APC such as macrophages and dendritic cells, and can avoid the carrier effects. Based on the characteristics of above-mentioned their properties differ from the bulk ones, Nanoparticulate alum adjuvant have been synthesized in the water-in-oil (w/o) microemulsion and preliminary assessed biology behavior as HBsAg vaccine adjuvant. At first, Maximum content of water of cation surfactant(BB)and cosurfactant (Oa) was studied, which was also the best r-matching(1:1) (w/w). It was slightly higher than theoretical 5:8. Then, the best r-matching of Oa-Bb/ cyclohexane/ AlCl3 water system on the formation of W/O microemulsion were discussed and draw the phase diagram. W/O microemulsion regions were the base part of the phase diagram. The proportion of microemulsion was the preparation formula. To assure nanoparticle produce and conside produce cost, content of water was the more, production was the more when oil content was fix. And the optimal conditions of preparation of W/O microemulsion were determined. By TEM photography for their texture, they were showed that the average particle d... |
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