Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Biomaterials. 2017 Dec;149:1-11. doi: 10.1016/j.biomaterials.2017.09.031. Epub 2017 Sep 26.

Active immunotherapy for TNF-mediated inflammation using self-assembled peptide nanofibers.

Author information

1
Department of Surgery, University of Chicago, Chicago, IL, 60637, United States; Molecular Pathogenesis Program, University of Chicago, Chicago, IL, 60637, United States.
2
Department of Surgery, University of Chicago, Chicago, IL, 60637, United States.
3
Molecular Pathogenesis Program, University of Chicago, Chicago, IL, 60637, United States.
4
Department of Chemistry, University of Virginia, Charlottesville, VA, 22904, United States.
5
Department of Surgery, University of Chicago, Chicago, IL, 60637, United States; Molecular Pathogenesis Program, University of Chicago, Chicago, IL, 60637, United States. Electronic address: joel.collier@duke.edu.

Abstract

Active immunotherapies raising antibody responses against autologous targets are receiving increasing interest as alternatives to the administration of manufactured antibodies. The challenge in such an approach is generating protective and adjustable levels of therapeutic antibodies while at the same time avoiding strong T cell responses that could lead to autoimmune reactions. Here we demonstrate the design of an active immunotherapy against TNF-mediated inflammation using short synthetic peptides that assemble into supramolecular peptide nanofibers. Immunization with these materials, without additional adjuvants, was able to break B cell tolerance and raise protective antibody responses against autologous TNF in mice. The strength of the anti-TNF antibody response could be tuned by adjusting the epitope content in the nanofibers, and the T-cell response was focused on exogenous and non-autoreactive T-cell epitopes. Immunization with unadjuvanted peptide nanofibers was therapeutic in a lethal model of acute inflammation induced by intraperitoneally delivered lipopolysaccharide, whereas formulations adjuvanted with CpG showed comparatively poorer protection that correlated with a more Th1-polarized response. Additionally, immunization with peptide nanofibers did not diminish the ability of mice to clear infections of Listeria monocytogenes. Collectively this work suggests that synthetic self-assembled peptides can be attractive platforms for active immunotherapies against autologous targets.

KEYWORDS:

Active immunotherapy; Adjuvant-free; Supramolecular; TNF; Vaccine

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center