用固相抗体-抗原复合物逆转对鸭乙型肝炎病毒的免疫耐受性

SOLID MATRIX ANTIBODY ANTIGEN(SMAA)COMPLEX CAN REVERT IMMUNE TOLERANCE VERSUS DUCK HEPATITIS B VIRUS INFECTION

目前我国有1亿乙型肝炎病毒(HBV)表面抗原(HBsAg)携带者,其中大多数系幼龄感染HBV,处于免疫耐受状态,而不能有效地产生免疫应答以清除病毒。我们用鸭乙型肝炎病毒(DHBV)感染1日龄幼鸭,获得DHBV DNA及病毒表面抗原(DHBsAg)持续阳性的动物模型,类似HBV的免疫耐受状态。为探讨逆转免疫耐受状态的途径,本文设计了改变DHBsAg的提呈方式,用固相抗体-抗原(Solid matrix antibody-antigen,SMAA)复合物给耐受动物注射,结果部分耐受鸭DHBsAg转阴,并出现了抗-DHBs。

One day old ducklings were experimentally infected with DHBV positive serum. Ducks that were persistently positive for serum DHBV DNA and DHBsAg up to 8 weeks, with no detectable anti-DHBS nor anti-DH Bc were accepted as immune tolerant ducks. As described by Randall, Staphylococcus Cowan I strain was used as the solid matrix, and high titer anti-DHBs/Pre-S serum was adsorbed to the matrix with subsequent attachment of the specific antigen to form SMAA. This SMAA complex was used to immunize immune tolerant ducks at 3μg antigen per duck with complete Freund adjuvant, at 3 week interval for 3 times. Three out of 7 tolerant ducks lost their serum DHBsAg while another 2 showed only trace of DHBsAg in their sera. Two remained DHBsAg positive. Among the 6 ducks examined for anti-DHBs, 4 were positive by ELISA. As controls, 7 tolerant ducks not immunized with SMAA remained DHBsAg positive. It is suggested that the presentation of antigen in an appropriate particulate form,with the presence of antibody bound antigen may be more easily processed. SMAA may trigger immunological reactions that can enhance the immune response. Future prospect of employing SMAA to re vertimmune tolerance versus human hepatitis B infection may be considered.