Synthesis Of Dendritic Macromolecules Based On Beta Cyclodextrin And Their Effects For Vaccine Adjuvant

Vaccine is important for the treatment of infectious diseases and potent diseases.Subunit vaccine,which is lack of virus genome,is with high security,but the immunogenicity of it is very weak,so we need to add a certain amount of vaccine adjuvant to improve the immune effect.This research aims to synthesize dendrimers based on ?-cyclodextrin,and to study its effect for immune adjuvant.First,?-cyclodextrin(?-CD)and methacrylic anhydride(MA)were used to synthesize?-cyclodextrin nucleus(?-CDMA),and the yield was 70%.Then,methacrylic anhydride and2-hydroxyethyl methacrylate were reacted to synthesize ethylene glycol dimethacrylate,and the yield was 71%.Taking ?-CDMA as the nucleus of the dendrimer,different generations of dendrimers were synthesized using ethylene glycol dimethacrylate and cysteamine.The yield of G1,G2,G3 dendrimers was 84%,80% and 90%,respectively.The 1H NMR results showed that the structure of synthesized compounds was correct.The gel permeation chromatography results showed that the polymer dispersibility index(PDI)of ?-CDMA was1.1,showing that ?-CDMA was homogeneous distributed and with high purity.For G1,G2 and G3 dendrimers,the molecular weight of the compounds was increased with the generation of the dendrimers,and PDI were all less than 1.1,showing that dendrimers were homogeneous distributed and with high purity.G3 dendrimer was used as an adjuvant for rubella subunit vaccine,while the aluminum adjuvant was the control group.The results of ELISA showed that the titer of antiserum was increased with the increase dosage of G3 dendrimer.The OD value of G3 dendritic macromolecule group and aluminum adjuvant group was compared under different dilution degrees of serum.When the dosage of adjuvant was 100 ?g,the serum dilution was 1: 160,1:320,the OD value of G3 dendritic macromolecule group was significantly higher than that of aluminum adjuvant group,which indicated that G3 dendrimer could improve the specific antibody titer of mouse serum.And 100 ?g dosage of G3 dendritic macromolecule group can stimulate the best immune effect.The concentration of IFN-?,IL-2 in secrum was detected,we found that when the dosage of adjuvant was 100 ?g,the concentration of IFN-?,IL-2 in G3 dendritic macromolecule group was higher compared with aluminum adjuvant group,indaicating that when the dose of G3 was 100?g,which was taken as an adjuvant,could improve the cellular immune response.The survival rate of T47 D cells was detected by MTT assay in vitro.The results showed that different concentration of G3 dendritic macromolecules did not induce cell death and could be used as an adjuvant.The above results indicate that G3 dendrimer is safe and effective as an adjuvant of rubella subunit vaccine,which is expected to lay the technical foundation for the prevention and treatment of rubella disease.