| Traditional virus vaccine is through the virus low temperature pass to get attenuated virus strains,and then amplified by the virus to obtain attenuated live vaccine,generally has a good immunogenicity.But with the development of time found that many live attenuated vaccines have virulence back to the ancestors and other phenomena,the developed countries are more inclined to use inactivated vaccine;with the development of molecular biology technology,the emergence of peptide vaccine,DNA vaccine,Unit vaccines,but inactivated vaccines,peptide vaccines,DNA vaccines,recombinant subunit vaccines are weak immunogenicity,theoretically need to add vaccine adjuvant,enhance the immunogenicity of these vaccines,the body to produce immune response in order to achieve the role of disease prevention and treatment.At present,aluminum adjuvant is widely used in human vaccine adjuvant,with cheap,safe,simple synthesis and so on.But there are still shortcomings,aluminum adjuvant small molecule antigen immune enhancement effect is not ideal;can only enhance the humoral immune response and can not enhance the cellular immune response;aluminum easy to accumulate in the body,especially in the brain,may lead to the occurrence of encephalopathy.Therefore,the development of safe and efficient new vaccine adjuvant is of great significance.INCB024360 as an anti-tumor drug has entered the second phase of clinical trials,as an IDO inhibitor can promote the growth of T cells,NK cells,reduce regulatory T cells(Treg),with a certain immune regulation.The INCB024360 analogue used in this study was an IDO inhibitor that was modified on the basis of INCB024360,with smaller molecular weight and inhibitory effect and better safety.Sodium polyphosphate as an important food additive has a high safety,can maintain protein water retention,delay the degradation of protein.Recent studies have found that polyphosphates are closely related to bone remodeling and bone metabolism,promoting fibroblast proliferation and maturation.The aim of this study was to investigate the effects of INCB024360 analogue combined with aluminum hydroxide and sodium polyphosphate as adjuvants on the humoral immune response induced by hepatitis A virus(HAV)in mice.In the experiment,5 different doses of INCB024360 analogue were combined with aluminum adjuvant(300 ?g),2 different doses of INCB024360 analogue combined with aluminum adjuvant(150 ?g),3 different doses of sodium polyphosphate(18 EU)antigen group,Al(OH)3(300 ?g)aluminum adjuvant control group,HepA-1(18 EU)antigen group,Al(OH)3(300 ?g)A single INCB024360 analogue(10 ?g)group was injected subcutaneously and immunized once again.Blood samples were collected at the 4th,8th,12th and 16th week after immunization.The anti-HAV antigen-specific IgG antibody was detected by ELISA Level.The results showed that INCB024360 analogue combined with aluminum hydroxide and sodium polyphosphate had some adjuvant effects,and the adjuvant effect increased with time,reached the peak at week 12,while the single INCB024360 analogue did not has a significant adjuvant effect.8 weeks,12 weeks,compound adjuvant 3[HepA-118 EU + Al(OH)3300 ?g+INCB024360 analogue 75 ?g]produced the highest antibody level and longer duration,8 weeks,12 weeks,(P<0.05,t = 2.448,2.482)was significantly higher than that in the control group(P<0.05).Compound adjuvant 4[HepA-118 EU +Al(OH)3150 ?g + INCB024360 analogue 125 ?g]antibody level with complex adjuvant 1[HepA-118 EU + Al(OH)3300 ?g + INCB024360 analogue 125 ?g]and the aluminum adjuvant group.At 12 weeks,the antibody level of sodium polyphosphate was significantly higher than that of aluminum adjuvant group(P<0.05).In this study,we found that IDO inhibitor INCB024360 analogue combined with aluminum adjuvant,sodium polyphosphate can enhance the immune response induced by hepatitis A antigen in mice,with immune adjuvant effect.The preliminary exploration of these two substances provides a new direction for the study of new vaccine adjuvants. |
PDF Full Text Request