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Effects Of Zoledronic Acid On Humoral Immune Response Induced By Hepatitis A Virus Antigen In Mice

Posted on:2015-07-30Degree:MasterType:Thesis
Country:ChinaCandidate:H J LiFull Text:PDF
GTID:2284330431472944Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
Vaccine adjuvants are defined as a kind of components that combine with antigen to enhance immune responses. Adjuvants can cause the body to produce long-term effective specific immune response, reduce antigen dose, and greatly expand vaccine supply. In recent years, because the rapid progress of biotechnology and genetic engineering, many new vaccines enter the market in succession, such as subunit vaccine, peptide vaccine, DNA vaccine and unique antibody vaccine etc. These vaccines antigens are relatively small molecular weight, low immunogenicity. It is difficult to induce effective immune response. For the purpose of enhancement the effectiveness of the antigen, the antigens need to mix with adjuvant to improve their ability to induce an immune response. The best vaccine adjuvants need to activate immune response at the same time vaccine adjuvants should have a stable, safe, non-toxic side effects. The equipment and process should be scalable, transferable and able to produce consistent batches.Until recently, Aluminum adjuvant is the first vaccine adjuvant for human, it may act by a combination of various mechanisms including formation of depot, adsorption antigen promote antigen present, stranded antigen, recruitment of immune cells, activate complement way. But through many years’ practice proved that aluminum adjuvant failed to stimulate an effective immune response when it mix with many recombinant or synthetic peptide vaccine antigen. In addition there will be local irritation, allergic reactions and can result the side effects such as neurodegenerative diseases. It’s difficult to meet the needs of the development of new vaccines. As the researchers of mechanism of adjuvant and the development of molecular biology, people will be more rational to choose the appropriate vaccine adjuvants, which is safe and effective, to prevention and treatment of disease. Application will be more safe and effective, therefore it is significance to develop the new immune adjuvant.ZOL is the third-generation bisphosphonate drugs which used to treat osteoporosis, bone metastases and hypercalcemia caused by a variety of solid tumors. ZOL can prevent cancer cells from producing a variety of stimulating factors, such as PG, TNF and IL-2, which induced the releasing of calcium ions and slow down the bone metastases. ZOL also can lead to the death of some tumor cells directly. In recent years, the study found that ZOL not only inhibit tumor and bone related diseases, but also can effect the body’s immune system, such as stimulating γδT lymphocyte proliferation, stimulate the mature of dendritic cells. Because ZOL can stimulate γδT cell proliferation, and secrete IFN-γ to regulate the immune system, so we speculated that the ZOL has the potential to be a novel adjuvants.In order to investigate the effect of the ZOL on humoral immune response induced by Hepatitis A antigen in mice. Experiment with different doses of ZOL were added into HAV antigen, mice were immunized by s. c. injection in several sites.And setting the physiological saline, adjuvant-free antigens, aluminum group. By indirect ELISA method to detect the mice serum anti HAV IgG, get a different point in time the experimental mice titer of anti-HAV IgG levels.The safety of the adjuvant was observed preliminarily.After preliminary study confirms the ZOL can enhance the effect of anti-HAV IgG level, ZOL group to the enhanced effect of humoral immunity of HAV antigen is obviously better than the HAV group (P<0.05), And it’s confirmed that the level of anti-HAV IgG of ZOL40ug group is the highest humoral immune-enhancing effects in ZOL experimental group, the enhanced effect of humoral immunity of HAV antigen is obviously better than the HAV group (P<0.05), close to aluminium group. Experimental period, there is no abnormal reaction in mice, pathological section shows that different organs were found lesions. It’s confirm that ZOL can enhance humoral immune response, ZOL has become a candidate vaccine adjuvant.
Keywords/Search Tags:Zoledronic Acid (ZOL), Adjuvant, Humoral immunity, HAV
PDF Full Text Request
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