期刊
ADVANCED HEALTHCARE MATERIALS
卷 3, 期 11, 页码 1898-1908出版社
WILEY
DOI: 10.1002/adhm.201400137
关键词
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资金
- NIH Tetramer Core Facility [HHSN272201300006C]
- NIH/NIAID [AI094444]
- NIH/NIBIB [EB009701]
- Bill & Melinda Gates Foundation [OPP1061315]
- Chicago Biomedical Consortium
- Searle Funds at The Chicago Community Trust
- Bill and Melinda Gates Foundation [OPP1061315] Funding Source: Bill and Melinda Gates Foundation
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 is 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 are 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 micromolar to millimolar elicited bell-shaped dose-responses that are unique to different T-cell populations. Notably, the epitope ratios that maximize 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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