Recent studies have investigated the potential of type 1 diabetes mellitus–related autoantigens, such as heat shock protein 60, to induce immunological tolerance or to suppress the immune response. A functional 24-residue peptide derived from heat shock protein 60 (P277) has shown anti-type 1 diabetes mellitus potential in experimental animals and in clinical studies, but it also carries a potential atherogenic effect. In this study, we have modified P277 to retain an anti-type 1 diabetes mellitus effect and minimize the atherogenic potential by replacing the P277 B epitope with another diabetes-associated autoantigen, insulinoma antigen-2 (IA-2), to create the fusion peptide IA-2-P2. In streptozotocin-induced diabetic C57BL/6J mice, the IA-2-P2 peptide displayed similar anti-diabetic effects to the control P277 peptide. Also, the IA-2-P2 peptide did not show atherogenic activity in a rabbit model. Our findings indicate the potential of IA-2-P2 as a promising vaccine against type 1 diabetes mellitus.

Objective To investigate the effects of an antidiabetic vaccine IA-2-P2 on atherosclerosis .Methods Twenty male rabbits were divided into three groups ,control ,hypercholesterolemic ,and hypercholesterolemic-IA-2-P2 groups ,receiving standard chow diet or high cholesterol diet for 17 weeks .The rabbits were immunized with PBS or IA-2-P2 emulsified in incomplete Freund Fre-und′s adjuvant 4 times at 4-week intervals .Serum lipid profiles were determined .At the end of the study ,aortic plaque formation was assessed .Results Compared with hypercholesterolemic group ,there were no significant difference on lipid profiles in hyper-cholesterolemic-IA-2-P2 group (P>0 .05) .The increases in lesion areas in the aorta were higher in hypercholesterolemic-IA-2-P2 than in hypercholesterolemic group ,without significant difference (P>0 .05) .Conclusion Our findings suggest that immunization with IA-2-P2 have some effects on atherosclerosis .

To study the hypoglycemic effect and mechanisms of vaccine HSP65-6P277 protein on type 1 diabetic mice induced by streptozotocin( STZ),Lactococcus lactis live vector was used to express the vaccine protein. The mouse model of type 1 diabetes mellitus were established by intraperitoneal injections of multiple low dose STZ( MLD-STZ) and divided into three groups. The inducible expression strain L. lactis NZ9000 pCYT ∶ HSP65-6P277,constitutive expression strain L. lactis NZ9000 pHJ ∶ HSP65-6P277 and control strains L. lactis NZ9000 pCYT ∶ Nuc were respectively immunized to diabetic mice orally once daily( 2 × 109CFU,200 μL) in the first week and once every week in the following weeks lasting for 16 weeks. Fasting blood glucose levels were measured once a month on blood samples taken from orbital venous plexus. Four months later,the mice were sacrificed. Spleen cell proliferation experiment was performed. IL-10 and IFN-γ cytokine levels of spleen cells and serum IgG levels were assayed using ELISA kits. The results showed that pCYT ∶ HSP65-6P277 group and pHJ ∶ HSP65-6P277 group have low blood glucose( P 0. 05),and maintain normal body weight,compared with control group( pCYT ∶ Nuc). On the other hand,cytokine IFN-γ levels were significantly lower( P 0. 05) in spleen cells supernatant and spleen cell proliferation was reduced against HSP65 and P277( P 0. 05),but serum IgG levels were not significantly different( P 0. 05).

IA-2-P2是由来自P277多肽的T表位与胰岛素瘤相关蛋白2(IA-2)的B表位组合而成的新疫苗肽,为验证其对1型糖尿病的治疗效果,采用多次小剂量注射链脲佐菌素(STZ)诱导C57BL/6雄性小鼠建立1型糖尿病模型,成模2w后,sc 100 μg多肽进行免疫治疗,间隔3 w免疫,共6次,每3 w收集被免疫动物的血清进行生化分析,测定血糖浓度和IgG抗体滴度并进行体重监测.结果显示IA-2-P2多肽能在一定程度上降低血糖,与对照组相比,IA-2-P2组终末平均血糖下降38％;并能维持小鼠的体重的稳定;多肽治疗能延长小鼠生存时间,在32 w观测期间,IA-2-P2组小鼠生存率达70％,较对照组40％的生存率有显著差异(P＜0.05);并且具有免疫调节作用,ELISA结果显示多肽可以有效引起免疫应答产生,与对照组相比,抗体水平有显著差异(P＜0.05).

Apratoxins are cytotoxic marine natural products isolated from cyanobacterium that had been prevented cotranslational translocation early in the secretory pathway and should be a potential anti-tumor drug.In recent years,lots of work has been carried out on their synthesis and pharmacological mechanism.A brief introduction on the research progress of Aparatoxins family was carried out.