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Zinc Hydroxide as a New Vaccine Adjuvant Enhance the Humoral Immune Response of HAV Antigen

Author: TaoLi
Tutor: HuYunZhang;HuNingZhu
School: Peking Union Medical College , China
Course: Biochemistry and Molecular Biology
Keywords: Zinc hydroxide Adjuvant Vaccine IgG IgE HAV
CLC: R392
Type: Master's thesis
Year: 2008
Downloads: 97
Quote: 1
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Abstract


Zinc is an essential trace element in all organisms. The growth and development of the human body can not be separated from the zinc, zinc levels in the body's level of be nervous, reproductive and immune system impact. The relationship between the zinc and the immune system is particularly complex, mainly reflected in the following four aspects: (1) daily zinc intake and the amount of absorption depends on the food component, individual age and health; (2) zinc having the biological activity of the enzyme cofactors as more than 300 kinds, it is possible to indirectly affect the immune system; (3) can have a direct effect of zinc on the generation, maturation and function of lymphocytes; (4) Zinc can affect the function of the immune enhancers. Take advantage of the characteristics of zinc above, used in the treatment of certain diseases, zinc preparation adjuvant therapy, that ordinary treatment given to patients with a certain dose of zinc preparations made good therapeutic effect. Have been observed in a number of clinical trials in infectious diseases, autoimmune diseases, vaccination to the positive role of zinc. The vaccine adjuvant is the current vaccine research development of hot spots, the ideal vaccine adjuvants need to have the safety, effective targeting and economic characteristics. Aluminum adjuvants only been approved for human vaccine adjuvant, which rely mainly on the storage effect and immunostimulating effect of both mechanisms, to significantly increase the body's immune response. However, as an adjuvant, which in terms of safety and targeting defective. Some other adjuvant effect of substance being studied or proven, due to the safety, effectiveness or economic issues, could not be approved for use in humans. Hydroxide, zinc hydroxide and aluminum hydroxide in the isoelectric point, water soluble, etc. having a high similarity, and the preparation process is simple, low cost. To this end, the study of this zinc salt as a research object, after repeated experiments, worked out the appropriate reactants and reaction conditions, the use of zinc acetate and ammonia prepared a detailed and uniform particles of zinc hydroxide product. Inactivated hepatitis A virus (Hepatitis A Virus, HAV) antigen group and HAV antigen aluminum adjuvant group, the control group, the use of different doses of zinc hydroxide inactivated HAV antigen hybrid immune ICR mice after immunization different time, detected by ELISA, the titer of the anti-HAV IgG in the mouse serum. The experimental results show that, starting from the first four weeks, the experimental group can produce anti-HAV antibodies, and both reached a peak in the first eight weeks. 1mg hydroxide immune effect of zinc group achieved within 28 weeks, the level of antibody titers were significantly higher than HAV group (P <0.05), and able to be maintained at a significantly higher level at 28 weeks, and except the first 8 weeks, the mice produced antibody titers are higher than the aluminum adjuvant group (P <0.05). After 12 weeks, the other dose groups had a the HAV group was significantly higher than the antibody levels. And Cap 4,24,28 weeks, most of the Zn adjuvant group antibody levels are higher than the aluminum adjuvant group (P <0.05). Proof zinc hydroxide have characteristics significantly improve the body's immune response. Aluminum adjuvants may attract eosinophils to the injection site, to increase the level and total IgE antibody specific antigen, and induction of IgE-mediated allergic reaction In order to determine the allergenicity of the zinc hydroxide, we obtain the best immune effects 1mg zinc hydroxide, mixed with 100μg of ovalbumin-sensitized BALB / c mice, and another mixed sensitized group of the same dose of the aluminum adjuvant ovalbumin IgE level generated by comparing the two, zinc adjuvant group after the first immunization The 8,14 day IgE levels were significantly lower than the aluminum adjuvant group (P <0.05). Safety trials showed that a portion of the aluminum adjuvant group mice depilation brain tissue pathological results show that a small amount of glial cell aggregation lesions, suggesting that there may be aluminum adjuvants on the nervous system damage; zinc hydroxide adjuvant group the liver, brain and kidney, the results were normal, suggesting the zinc hydroxide security superior to aluminum adjuvant. At home and abroad for the first time, we have found that zinc hydroxide efficient stimulation of the immune response, hypoallergenic and low toxicity of adjuvant characteristics, provides a new way of thinking for the research and development of novel vaccine adjuvant.

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