| With the rapid development of modern biological technology in recent years, recombinant subunit vaccines, anti-idiotypic antibodies, nucleic acid vaccine and its synthetic peptide vaccines are developed. These vaccines antigens are of high purity, and relatively small molecular weight, low adverse vaccine reactions, however, the immunogenicity of these antigens are generally weak. In order to improve the effectiveness of the antigen, the antigen need to add adjuvant to enhance their ability to induce an immune response. At present, not many vaccine adjuvants approved for human body, the classic aluminum adjuvant is one of them, and aluminum adjuvant was the only globally recognised in vaccine adjuvants used in human. But years of practice has proved that aluminum adjuvant failed to stimulate an effective immune response to low molecular weight antigen. At the same time, aluminum adjuvant may cause local irritation response and adverse reactions. What’s more, aluminum adjuvant may also lead to encephalopathy. As a result, to find safer and more effective adjuvants is significant.This research is aimed to study the effects of DFO and NaHS on humoral immune response induced by HAV antigens. With a good security, DFO is used to treat diseases which induced by overloaded Iron ions. H2S, together with nitric oxide (NO) and CO, belongs to a family of labile biological mediators termed gasotransmitters, which share many similarities. Widely existing in mammals, H2S was identified as an important cell signaling molecule and plays a pivotal role in the cardiovascular and nervous system. As a donor of H2S, NaHS can dissociate into H2S and free sodium ions. In normoxia conditions, both of DFO and NaHS can promote the stabilization of HIF-1and improve the transcriptional activity of the downstream gene of HIF-1through binding the enhancer. The ability of HIF-1to regulate its target genes is dependent on the oxygen concentration in cells. It is revealed that immune cells is often in a physiological and pathological hypoxia condition which influence many biologic functions of the immune cells, including improved adaptive capacity of the effective cells in immune system in energy metabolism side and their normal functions. As a transcription factor, HIF-1plays an important role in regulating immune cells in hypoxia condition.This study is to investigate the effect for the DFO and NaHS on humoral immune response induced by Hepatitis A antigen in mice and to make a preliminary discussion of being vaccine adjuvant potential of DFO and NaHS. In this study, ICR mice were immunized with the mixture of different doses of DFO and HAV antigen or the mixture of different doses of NaHS and HAV antigen. ICR mice were immunized with the mixture that physiological saline, adjuvant-free HAV antigen, and aluminum hydroxide adjuvant as control, DFO and aluminum adjuvant, NaHS and aluminum adjuvant. DFO and NaHS adjuvant, DFO and NaHS groups. Anti-HAV IgG was examined by indirect ELISA at different time.The study was approved with preliminarily that DFO and NaHS can significantly enhance the humoral immune response of mice induced by HAV. The results show that the level of anti-HAV IgG of DFO4mg and DFO8mg groups are the highest humoral immune-enhancing effects in DFO experimental group, which are better than the control groups of adjuvant-free antigen group and have a statistical significance (P<0.05), but compared to aluminum adjuvant control, there is no statistical significance (P>0.05). It’s confirmed that the level of anti-HAV IgG of NaHS3umol and NaHS14umol groups are higher than the adjuvant-free antigen group at the time examined and the difference have a statistical significance (P<0.05). And NaHS and aluminum adjuvant group’s effect of enhancing humoral immune response is significantly higher than the adjuvant-free antigen group with a statistical significance (P<0.05). And this effect is higher than the aluminum adjuvant control at the16th week with a statistical significance (P<0.05).In adjuvant safety testing, pathological section of DFO and NaHS of highest dose mice and10mg/dose of BALB/C mice were not found abnormal. Mouse does not appear period tremble, seizures, convulsions, shortness of breath, edema and shock in the test; Eat, excretion and spirit were not found abnormal; Injection site no swelling, nodules. Study results showed that DFO and NaHS have good security and no obvious toxicity during the experiment.In this experiment, we found that DFO and NaHS can effectively enhance the humoral immune response, and these two substances with aluminum adjuvant compound exhibit different synergies. The studies provide new directions for new vaccine adjuvant research. We will do further research about cellular immune effect on these new adjuvants to provide support of experimental data in the future?... |
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