Titrating T-cell epitopes within self-assembled vaccines optimizes CD4+ helper T cell and antibody outputs.
Adv Healthc Mater
; 3(11): 1898-908, 2014 Nov.
Article
in En
| MEDLINE
| ID: mdl-24923735
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
CD4-Positive T-Lymphocytes
/
Th2 Cells
/
Th1 Cells
/
Epitopes, T-Lymphocyte
/
Antibodies
Limits:
Animals
/
Humans
Language:
En
Journal:
Adv Healthc Mater
Year:
2014
Document type:
Article
Affiliation country:
Estados Unidos