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

TitleTitrating T-cell epitopes within self-assembled vaccines optimizes CD4+ helper T cell and antibody outputs.
Publication TypeJournal Article
Year of Publication2014
AuthorsPompano, RR, Chen, J, Verbus, EA, Han, H, Fridman, A, McNeely, T, Collier, JH, and Chong, AS
JournalAdvanced healthcare materials
Volume3
Issue11
Start Page1898
Pagination1898 - 1908
Date Published11/2014
Abstract

<p>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.</p>

DOI10.1002/adhm.201400137
Short TitleAdvanced healthcare materials