Titrating T-cell epitopes within self-assembled vaccines optimizes CD4+ helper T cell and antibody outputs.
Titrating T-cell epitopes within self-assembled vaccines optimizes CD4+ helper T cell and antibody outputs.
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DOI：
10.1002/adhm.201400137
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发表时间：
2014-11
影响因子：
10
通讯作者：
Chong, Anita S.
中科院分区：
文献类型：
--
作者：
Pompano, Rebecca R.;Chen, Jianjun;Verbus, Emily A.;Han, Huifang;Fridman, Arthur;McNeely, Tessie;Collier, Joel H.;Chong, Anita S.
表位含量在决定T细胞和抗体对疫苗、生物材料和蛋白质疗法的反应中起着关键作用，但其作用是非线性的，难以分离。在这里，分子自组装被用来构建一种精确控制表位内容的疫苗，以便精细地调节T辅助和抗体反应的大小和表型。通过高亲和力的通用CD4+ T细胞表位（PADRE）和来自金黄色葡萄球菌的B细胞表位在特定浓度下的共组装，形成了自佐剂肽纳米纤维。将PADRE浓度从μM增加到mM，会引起不同T细胞群特有的钟形剂量反应。值得注意的是，最大化T滤泡辅助细胞和抗体应答的表位比率与最大化Th1或Th2应答的表位比率相差一个数量级。因此，模块化材料组装提供了一种在缺乏外源性佐剂的情况下控制表位含量和有效地扭曲适应性免疫反应的手段；这种方法可能有助于改进疫苗和免疫疗法的发展。
Epitope content plays a critical role in determining T cell and antibody responses to vaccines, biomaterials, and protein therapeutics, but its effects are nonlinear and difficult to isolate. Here, molecular self-assembly was used to build a vaccine with precise control over epitope content, in order to finely tune the magnitude and phenotype of T helper and antibody responses. Self-adjuvanting peptide nanofibers were formed by co-assembling a high-affinity universal CD4+ T cell epitope (PADRE) and a B cell epitope from Staphylococcus aureus at specifiable concentrations. Increasing the PADRE concentration from μM to mM elicited bell-shaped dose-responses that were unique to different T cell populations. Notably, the epitope ratios that maximized T follicular helper and antibody responses differed by an order of magnitude from those that maximized Th1 or Th2 responses. Thus, modular materials assembly provides a means of controlling epitope content and efficiently skewing the adaptive immune response in the absence of exogenous adjuvant; this approach may contribute to the development of improved vaccines and immunotherapies.
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DOI：
10.1073/pnas.73.10.3671
发表时间：
1976-01-01
影响因子：
11.1
作者：
DINTZIS, HM;DINTZIS, RZ;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
--
作者：
Aggeli, A;Bell, M;Semenov, A
通讯作者：
Semenov, A
影响因子：
6.1
作者：
Barwig, C.;Raker, V.;Sudowe, S.
通讯作者：
Sudowe, S.
DOI：
10.4049/jimmunol.0901957
发表时间：
2009-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kaba SA;Brando C;Guo Q;Mittelholzer C;Raman S;Tropel D;Aebi U;Burkhard P;Lanar DE
通讯作者：
Lanar DE