A novel C3d-containing oligomeric vaccine provides insight into the viability of testing human C3d-based vaccines in mice.
A novel C3d-containing oligomeric vaccine provides insight into the viability of testing human C3d-based vaccines in mice.
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DOI：
10.1016/j.imbio.2017.10.002
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发表时间：
2018-01
期刊：
影响因子：
2.8
通讯作者：
Marchbank KJ
中科院分区：
文献类型：
--
作者：
He YG;Pappworth IY;Rossbach A;Paulin J;Mavimba T;Hayes C;Kulik L;Holers VM;Knight AM;Marchbank KJ
C3d，补体蛋白C3的最终降解产物，作为一种“天然”佐剂的使用已经被广泛研究，因为它的免疫原性增强特性的最初文件作为结合补体受体2的结果。随后证明，当C3d的寡聚体而不是单体形式与各种测试蛋白抗原连接时，这些效应最明显。在这项研究中，我们研究了利用C4b结合蛋白（C4BP）提供一个寡聚体阵列支架融合到模型抗原，破伤风毒素C片段（TTCF），进一步增强人C3d的佐剂特性的可行性。高分子量，C3d的寡聚体疫苗成功地表达，从哺乳动物细胞纯化，并用于免疫组小鼠。令人惊讶的是，在这些小鼠中测量的抗TTCF抗体应答很差。随后，我们通过体外和体内分析确定，在小鼠C3的存在下，人C3d不与小鼠甚至人补体受体2相互作用。这些数据证实了需要开发基于C3d的佐剂化合物的鼠版本以在小鼠中测试，或者需要开发表达人C3和人CR 2两者的小鼠以允许以任何能力在小鼠中测试基于人C3d的佐剂。
The use of C3d, the final degradation product of complement protein C3, as a “natural” adjuvant has been widely examined since the initial documentation of its immunogenicity-enhancing properties as a consequence of binding to complement receptor 2. Subsequently it was demonstrated that these effects are most evident when oligomeric, rather than when monomeric forms of C3d, are linked to various test protein antigens. In this study, we examined the feasibility of enhancing the adjuvant properties of human C3d further by utilizing C4b-binding protein (C4BP) to provide an oligomeric arrayed scaffold fused to the model antigen, tetanus toxin C fragment (TTCF). High molecular weight, C3d-containing oligomeric vaccines were successfully expressed, purified from mammalian cells and used to immunize groups of mice. Surprisingly, anti-TTCF antibody responses measured in these mice were poor. Subsequently we established by in vitro and in vivo analysis that, in the presence of mouse C3, human C3d does not interact with either mouse or even human complement receptor 2. These data confirm the requirement to develop murine versions of C3d based adjuvant compounds to test in mice or that mice would need to be developed that express both human C3 and human CR2 to allow the testing of human C3d based adjuvants in mouse in any capacity.
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影响因子：
56.9
作者：
HEBELL, T;AHEARN, JM;FEARON, DT
通讯作者：
FEARON, DT
影响因子：
3.6
作者：
Kulik, Liudmila;Chen, Kuan;Holers, V. Michael
通讯作者：
Holers, V. Michael
DOI：
10.1073/pnas.78.3.1828
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LAMBRIS, JD;DOBSON, NJ;ROSS, GD
通讯作者：
ROSS, GD
影响因子：
56.9
作者：
Dempsey, PW;Allison, MED;Fearon, DT
通讯作者：
Fearon, DT
影响因子：
5.4
作者：
ERDEI, A;MELCHERS, F;DIERICH, M
通讯作者：
DIERICH, M