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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Pompano, RR; Chen, J; Verbus, EA; Han, H; Fridman, A; McNeely, T; Collier, JH; Chong, AS

Published Date

  • November 2014

Published In

Volume / Issue

  • 3 / 11

Start / End Page

  • 1898 - 1908

PubMed ID

  • 24923735

Electronic International Standard Serial Number (EISSN)

  • 2192-2659

International Standard Serial Number (ISSN)

  • 2192-2640

Digital Object Identifier (DOI)

  • 10.1002/adhm.201400137

Language

  • eng