|Title||Titrating T-cell epitopes within self-assembled vaccines optimizes CD4+ helper T cell and antibody outputs.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||RR Pompano, J Chen, EA Verbus, H Han, A Fridman, T McNeely, JH Collier, and AS Chong|
|Journal||Advanced Healthcare Materials|
|Pagination||1898 - 1908|
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.
|Short Title||Advanced Healthcare Materials|