Research On The Adjuvant Effect Of Compound Uniting IDO Inhibitor And Aluminum Hydroxide

Background Modern new adjuvants can remedy the deficiency of traditional adjuvents,meanwhile,they have advantages in releasing antigen slowly and promoting broader immune responses which also induce stronger immune reaction by uniting adjuvants.However the adjuvants compounded simply cannot overcome the technical problems of single adjuvant,thus searching for new adjuvants is still urgent.Indoleamin-2,3 dioxygenase(IDO)can lead to vaccine tolerance by its immunosuppressive effect which also can affect the role of adjuvants in immune response.So its inhibitors can improve vaccination effect which combined with aluminum hydroxide also will enhance the antibody lever both by promoting positive regulation and inhibiting negative feedback.The combination of the two can be a potential compound adjuvant candidate.Objective This experiment aim to investigate the IDO inhibitors[4-phenylimida zole(4-PI)and Rosmarinic acid(RosA)]combined with aluminum hydroxide influence on the mice humoral immunity induced by live hepatitis A virus attenuated live vaccine(HepA-1).Method Mice were immunized with the conpound adjuvant which composed of HepA-l,Al(OH)3 and different doses of 4-PI/RosA.1×phosphate buffer saline group,antigen group,aluminum adjuvant group,single 4-PI or RosA adjuvant group were set as control group.The specific antibody level of anti-HAV were tested by ELISA to evaluate the effect of the compound adjuvants and the single inhibitors.Results The results suggest that the anti-HAV IgGs of compoud 4-PI 1 mg group,compound RosA 400 p.g group were significantly higher than that of other groups.There is statistic difference in single inhibitor group,antigen group and aluminum adjuvant group respectively(P<0.05).The IgGs of different dose compound adjuvant groups were also higher than that of antigen group in different time point.The IgG titers of single 4-PI,RosA group were equal to that of antigen group respectively,the adjuvant effect is moderate.The IgGs of aluminum adjuvant group were higher than that of antigen group,but there is no statistic significance.The optimal dose of 4-PI is 1 mg per mouse,RosA is 400 ?g per mouse.Conclusion The experimental results indicate that 4-PI+Al(OH)3 and RosA+Al(OH)3 compounds can enhance humoral immune response induced by HepA-1 in mice and prove the rationality and effectiveness to take IDO as a target adjuvant.IDO inhibitors have the potential to be a new adjuvant.Our research build basis for selection and design of this adjuvant.