Cationic lipid DC-Chol induces an improved and balanced immunity able to overcome the unresponsiveness to the hepatitis B vaccine

Cationic lipid DC-Chol induces an improved and balanced immunity able to overcome the unresponsiveness to the hepatitis B vaccine
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DOI:
10.1016/s0264-410x(98)00492-7
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发表时间:
1999-04-23
期刊:
影响因子:
5.5
通讯作者:
Ronco, J
Ronco, J
中科院分区:
医学3区
文献类型:
--
作者:
Brunel, F;Darbouret, A;Ronco, J

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针对抗原的Th 1和Th 2免疫应答可通过使用佐剂来调节。由于抗体同种型(IgG 1和IgG 2a)和细胞因子的诱导可能反映了免疫应答过程中Th细胞的分化。当抗原吸附于氢氧化铝或与新型佐剂3 β-[N-(N ',N'-二甲基氨基乙烷)氨基甲酰基]胆固醇(DC-Chol)一起给药时,检测了小鼠对B病毒表面抗原(HBsAg)诱导的体液和细胞免疫应答。DC-Chol的使用增加了应答BALB/ c小鼠的抗体应答,在OF 1小鼠中诱导了更一致的IgG 1和IgG 2a抗体应答,并克服了B10.M小鼠对HBsAg的无应答。此外,DC-Chol能够诱导对HBsAg的细胞免疫应答。DC-Chol诱导了平衡的Th 1/Th 2应答,这使得小鼠能够克服铝佐剂疫苗遇到的对HBsAg的遗传性无应答性。因此,DC-Chol提供了一个信号来启动Th 1和Th 2应答,这可能对针对B型肝炎病毒的疫苗接种以及增强无应答人群中其他重组纯化抗原的弱免疫原性具有重要意义。(C)1999 Elsevier Science Ltd.保留所有权利。
Th1 and Th2 immune responses against antigens can be modulated by the use of adjuvants. Since antibody isotypes (IgG1 and IgG2a) and cytokines induced may reflect the Th differentiation taking place during the immune response, the humoral and cellular immune responses induced in mice against hepatitis B virus surface antigen (HBsAg) were examined when the antigen was either adsorbed to aluminum hydroxyde or administered with a new adjuvant the cationic lipid 3 beta-[N-(N',N'-dimethylaminoethane)carbamoyl]cholesterol(DC-Chol). The use of DC-Chol increased antibody responses in responding BALB/ c mice, induced more consistent IgG1 and IgG2a antibody responses in OF1 mice and overcame the nonresponse to HBsAg in B10.M mice. Furthermore, DC-Chol was able to induce cellular immune responses to HBsAg. The DC-Chol induced a balanced Th1/Th2 response, which enabled mice to overcome the inherited unresponsiveness to HBsAg encountered with aluminum-adjuvanted vaccine. Thus, the DC-Chol provides a signal to switch on both Th1 and Th2 responses, which may have important implications for vaccination against hepatitis B virus, as well as for enhancing weak immunogenicity of other recombinant purified antigens in a nonresponder population. (C) 1999 Elsevier Science Ltd. All rights reserved.