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Adv Healthc Mater. 2014 Nov;3(11):1898-908. doi: 10.1002/adhm.201400137. Epub 2014 Jun 13.

Titrating T-cell epitopes within self-assembled vaccines optimizes CD4+ helper T cell and antibody outputs.

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Department of Surgery, Committee of Immunology, University of Chicago, 5841 S. Maryland Avenue, MC5032, Chicago, IL, 60637, USA.


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.


MRSA; co-assembly; immunoengineering; scaffolds; self-adjuvanting

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