ASDP/ASDE3作为乙型肝炎基因工程疫苗新型复合佐剂的效果及安全性

STUDIES ON ADJUVANT ACTIVITY AND SAFETY OF A NEW IMMUNOADJUVANT, ASDP/ASDE3, OF RECOMBINANT HEPATITIS B VACCINE

以中药当归[Angelica sincnsis(Oliv) Diels]研制的新型复合免疫佐剂——ASDP/ASDE3与哺乳动物细胞系表达的重组乙型肝炎病毒表面抗原(HBsAg)合用,经动物试验表明,其免疫佐剂效果明显优于现用的氢氧化铝胶佐剂,免疫动物血清抗-HBs水平及阳转率均比后者高,且疫苗的ED50可降低3～4倍。动物多途径局部及整体给药的急性毒性试验均显示毒性很小,说明ASDP/ASDE3是一种值得深入研究的新型免疫佐剂。

A new immunoadjuvant, ASDP/ASDE3, tested with recombinant hepatitis B surface antigen ( HBsAg ) vaccine was reported. It is derived from the Chinese traditional tonic medicine, Angelica sinensis (Oliv. ) Diels by chemical extraction and purification.The immunoadjuvant activity of ASDP/ASDE3 is significantly higher than that of aluminium hydroxide gel used as a control in a number of parameters. The ED50 of anti-HBs conversion was 2-4 folds smaller than that of aluminium hydroxide. The anti-HBs titers were at least 20 folds higher.The acute toxicity ( LD50 ) of new immuno-adjuvamt in mouse by subcutaneous, intramuscular and intravenous injection are >2,000mg/ kg, 800mg/kg and 200mg/kg respectively.No marked pathological changes and tissue damages were observed after local administration of ASDP/ASDE3 by various routes.ASDP/ASDE3 did not induce type I allergic reaction in mice and guinea pigs.It can activate the lysosomyl enzymes ( acidic phosphatase, N-ace-tylamino-glucosidase ) and modulate the membrane enzymes ( alkaline phosphatase and alkaline phosphodiesterase ) of peritoneal macrophage of mice in vivo.ASDP/ASDE3 is a new adjuvant with high efficacy and low toxicity. Chinese traditional medicine may be a new approach to the further study and development of new immunoadjuvant.