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Preparation Of New Vaccines Adjuvant Zinc Hydroxide And The Immune-enhancing Effect Of The ATP-aluminum, The ATP-zinc Compound Adjuvant

Posted on:2013-07-23Degree:MasterType:Thesis
Country:ChinaCandidate:H ZhangFull Text:PDF
GTID:2284330431975862Subject:Biochemistry and Molecular Biology
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The development of vaccine adjuvants has been impacted on the application of new vaccines directly. In order to develop a vaccine adjuvant that more secure, efficient, economic and more targeted than even before, researchers conducted a large number of studies. But for now, the aluminum adjuvant is still the most popular vaccine adjuvant. It can significantlyenhance the effect of the vaccine in the body, mainly dependent on mechanism of action of "the repository effects" and "the immune-stimulating effects". Although there is some mildallergic reactions, but overall, it’s safety and effectiveness has been confirmed after decades of applications.Zinc is one of the essential trace elements, It is closely related to people’s health. The body’s zinc levels could impact on nervous, reproductive and immune systems. For the complex relationship between zinc and immune system, zinc is more widely used in the treatment of some diseases. Because of the similar physical and chemical properties between zinc hydroxide and aluminum hydroxide. Just like aluminum,zinc hydroxide can exist astable as colloidal solution under certain conditions. For the aluminum adjuvants have achieved good results in clinical applications, zinc hydroxide is hoped as a excellent vaccine adjuvant in future researches. Besides, the safety and efficacy of zinc hydroxide adjuvant also has been initially confirmed in preliminary studies. In this study, with reference to the preparation method of aluminum adjuvants. First of all, put the zinc gluconate and low concentrations of sodium hydroxide solution, to prepar a stable zinc hydroxide colloidal solution. And then, accordance with the requirements of the production of vaccine adjuvants, make some improvements of its physical and chemical properties. Finally, we get the zinc hydroxide colloidal solution which can be used as a vaccine adjuvant.Adenosine triphosphate disodium (ATP) is a kind of coenzyme. ATP is the main source of energy in the body, and it also plays an important role in immune responses. The experiments showed that ATP can make some impact on the expres levels of IgG, IgA, and IgM in vivo when it used composite with MgCl2. At the same time, It’s an important class of endogenous danger signal factor in vivo. ATP levels change often implies organization hypoxiad,damaged or lesionsed. Based on these feature, change the ATP level under certain conditions can effectively activate the immune system. Therefore, ATP also be further developmented and research as a potential vaccine adjuvant.The Compound Adjuvant is one of the new reserch spot in these years. For the effect of vaccine adjuvants separately used is not ideal, and combined use a variety of vaccine adjuvants can achieve satisfactory results. There are many deepening researches on compound adjuvant. In this study, we use the aluminum adjuvant which has been extensive used, and the zinc hydroxide colloid adjuvant which prepared during the experiments, to mixed with ATP respectively to prepare the compound adjuvants. And then, make some researches on the effect of differences between composite adjuvanted and aluminum or zinc adjuvant used alone. During this research, we use the rabies vaccine as antigen, and set the groups with control group which with non-adjuvanted antigen, the single-adjuvant groups which added aluminum or zinc adjuvant alone, and the compound adjuvant groups which added the ATP-aluminum hydroxide compound adjuvant or the ATP-zinc hydroxide compound adjuvant. Each groups immunization of ICR mice,and on the different time periods after the initial immunization, detection of serum anti-rabies virus IgG titer by indirect ELIS A.Humoral immune effect evaluation showed that the effect of Zn(OH)2colloid is similar to the aluminum adjuvant. It could enhance the body immune response against rabies virus antigen to some extent.both when it used alone and conjunction with ATP. Although adjuvant immunohistochemical not reached the antigen immunohistochemistry (antigen control group IV) effect yet (P<0.05), but the antibody level has been higher than1-3times immunohistochemistry (antigen control I, II, III group)(P<0.05). The results tips that both Zn(OH)2colloid adjuvant used alone and conjunction with ATP can enhance the rabies vaccine specific humoral immune response. Through the horizontal comparison it can be found that the effect of zinc hydroxide colloids used as an adjuvant has been close to or even above the aluminum adjuvant.Beside this, the toxicity of zinc is lower than the aluminum element. The development and application of zinc adjuvant is also expected to overcome the bottleneck of the application of aluminum adjuvants, to be more promising.
Keywords/Search Tags:Aluminum adjuvant, Zinc hydroxide colloids, Compound adjuvant, Rabiesvaccine, Immunity
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