Mouse strain-dependent differences in enhancement of immune responses by C3d.
Mouse strain-dependent differences in enhancement of immune responses by C3d.
复制标题
C3d 增强免疫反应的小鼠品系依赖性差异。
DOI：
10.1016/j.vaccine.2003.10.050
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Ross,TedM
中科院分区：
文献类型：
--
作者：
Toapanta,FranklinR;Ross,TedM
我们的实验室已经证明，将补体蛋白C3 d与抗原结合是一种有效的方法，可引发高滴度、持久的抗体。使用C3 d作为分子佐剂在增强表达人免疫缺陷病毒（HIV）的包膜（Env）蛋白的DNA疫苗的功效方面是相当有效的。然而，我们以前的研究已经检查了C3 d结合疫苗在BALB/c小鼠中的有效性。在这项研究中，一个远交系和三个不同的近交系小鼠接种质粒表达的分泌形式的Env（sgp 120）融合到两个或三个拷贝的小鼠同源C3 d（mC 3d）。滴度分析表明，与C3 d的多个拷贝缀合的sgp 120在所有测试的小鼠品系中诱导相似的高滴度抗Env抗体。而免疫近交系小鼠的免疫球蛋白亚类主要为IgG 1，免疫远交系小鼠的免疫球蛋白亚类为IgG 1和IgG 2的混合物。此外，来自所有sgp 120-mC 3d-DNA接种的近交系小鼠品系的脾细胞主要分泌白细胞介素-4（IL-4），表明T辅助细胞（Th）2型应答。相比之下，用sgp 120-mC 3d-DNA接种的小鼠具有分泌IL-4和干扰素-γ（INF-γ）的脾细胞，表明混合的T辅助应答。此外，在具有表达sgp 120-mC 3d的DNA的远交小鼠中，抗Env抗血清的亲合力成熟增强。总体而言，与近交系小鼠相比，C3 d缀合的DNA疫苗在远交系小鼠中引起增强的免疫应答。
Our laboratory has demonstrated that conjugating the complement protein, C3d, to an antigen is an effective method for eliciting high titer, long-lasting antibodies. The use of C3d as a molecular adjuvant is quite effective in enhancing the efficacy of DNA vaccines expressing the envelope (Env) protein of the human immunodeficiency virus (HIV). However, our previous studies have examined the effectiveness of C3d conjugated vaccines in BALB/c mice. In this study, one outbred strain and three different inbred strains of mice were vaccinated with plasmids expressing a secreted form of Env (sgp120) fused to two or three copies of the murine homologue of C3d (mC3d). Analyses of titers demonstrated that sgp120 conjugated to multiple copies of C3d induced similar high titer anti-Env antibodies in all mouse strains tested. However, the immunoglobulin subclass elicited in inbred mice vaccinated with sgp120-mC3d-DNA was predominately IgG1, but was a mixture of IgG1and IgG2ain vaccinated outbred mice. Also, splenocytes from all sgp120-mC3d-DNA vaccinated inbred mouse strains secreted primarily interleukin-4 (IL-4) indicating a T helper (Th) type 2 response. In contrast, mice vaccinated with sgp120-mC3d-DNA had splenocytes that secreted both IL-4 and interferon-gamma (INF-γ) indicating a mixed T helper response. In addition, the avidity maturation of the anti-Env antisera was enhanced in outbred mice with DNA expressing sgp120-mC3d. Overall, C3d conjugated DNA vaccines elicited enhanced immune responses in outbred mice compared to inbred mice.