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Endogenous Danger Signal Low Molecular Weight Hyaluronan as New Vaccine Adjuvant

Author: ShuXiaoMing
Tutor: HuYunZhang；HuNingZhu
School: Peking Union Medical College , China
Course: Biochemistry and Molecular Biology
Keywords: Endogenous danger signals Adjuvant Hepatitis B surface antigen Hepatitis A antigen Nanospheres Cellular immunity
CLC: R392
Type: Master's thesis
Year: 2008
Downloads: 100
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Abstract

Infectious diseases such as HBV, HCV, HIV, and tumor global spread to the widest range of affected populations most important diseases of serious harm to human health. The prevention and treatment of infectious diseases and tumors are the most effective and most economical means of vaccination. The vaccines include in preventive vaccines and therapeutic vaccines. The present study, genetically engineered vaccines, subunit vaccines, synthetic peptide antigen vaccine immunogenicity, and vaccine being offered poor targeting. This need to give the vaccine, particularly a therapeutic vaccine adjuvants to enhance the vaccine antigen-specific humoral and cellular immune response CTL (cytotoxic T lymphocyte), and thus play both preventive and also treatment of viral infections, of neoplastic diseases. The vaccine adjuvant to selectively stimulate the immune response and improve the immune effect. However, most current vaccine adjuvant can only induce humoral immune response, the immune effector cells generated less or even no. Therefore, there is an urgent need to develop a new type of human vaccine adjuvant, antigen immunogenic so that it can effectively improve the processing of exogenous antigen presenting pathway to enhanced cellular immune responses, and through cross. In order to better explain the immune recognition mechanisms, Polly Matzinger in 1994 raised the danger signal mode theory, in this mode, the function of the immune system is involved in identifying the danger signal molecules and non-hazardous signaling molecules. Cell injury can be the risk of the release of signaling molecules to activate antigen-presenting cells (Antigen Presenting Cells, APCs) Further the effective activation of T / B cell to produce a corresponding immune response. This also shows that the danger signal molecules released by damaged cells have the potential immune adjuvant effect. Endogenous danger signal having a characteristic cross-antigen presentation to induce cellular immunity, suggesting that endogenous danger signal inducing specific cellular immune response can be used as a therapeutic vaccine adjuvant. In this study, for the first time selected endogenous danger signals - extracellular matrix degradation products of low molecular weight hyaluronic acid as a novel vaccine adjuvant, low molecular weight hyaluronic acid molecular weight <10 ^{6 ; respectively with HAV mixed immune ICR mice; antigen and HBV antigen and Let HAV, HBV separate antigen by immunohistochemistry and Al (OH) ₃ adjuvant control group. Anti-HAV-IgG, anti-HBV-IgG antibody titers and CTL cell immune effector different time anti-HAV-IgG and anti-HBV-IgG antibody titers and CTL cytotoxic activity was detected by ELISA and LDH. In addition, we also selected 2.0mg low molecular weight hyaluronic acid HBV antigen immunohistochemistry aluminum adjuvants and set to the control group in the seventh day of blood sampling to detect anti-HBV antibody titers after immunization, specific anti-HBV IgG levels were 1:30.84 ± 1.43, while both of the conventional aluminum adjuvant group 1:9.46 ± 3.99 compared to a statistically significant (P <0.05). In this study, preliminary endogenous danger signal molecules of low molecular weight hyaluronic acid can significantly enhance the results of HAV antigen and HBV antigen antibody levels and HBV antigen CTL cell immune effector. And confirmed that the endogenous danger signal molecules of low molecular weight hyaluronic acid produced anti-HAV IgG and anti-HBV IgG antibody levels were significantly higher than aluminum adjuvant group (P <0.05). In addition, the low molecular weight hyaluronic acid produced antibody levels earlier than the aluminum adjuvant. In addition, we used a low molecular weight hyaluronic acid into nanospheres were prepared and package the HBV antigen ICR mice. Preliminary exploration of its immune-enhancing effects, found that non nanospheres experimental group and the conventional aluminum adjuvant group compared to low molecular weight hyaluronic acid nanospheres significantly enhance the level of anti-HBV-IgG (P <0.05). We also found that the safety tests of the adjuvant, the mice in the group of conventional aluminum adjuvants appears to hair loss, pathological findings, parenchymal microglia Summary, suggesting that aluminum adjuvants there may be damage to the nervous system, liver and kidney no abnormalities; while the experimental group and the packet of the low molecular weight hyaluronic acid is of HBsAg nanospheres toxicity test of the experimental group and anaphylaxis experimental low molecular weight hyaluronic acid was not observed in the abnormal reaction. Liver, brain and kidney results were normal. This prompted: low molecular weight hyaluronic acid is safe and non-toxic, and may be suitable should be others. In short, in the present experiments, we found that the low molecular weight hyaluronic acid as adjuvant, both effectively enhance the specific humoral immune response, but also a significant CTL cells induced by immune effector; Further, prepared nanospheres can also significantly induced generating a strong immune effector.}

Endogenous Danger Signal Low Molecular Weight Hyaluronan as New Vaccine Adjuvant

Abstract

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