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

Area of Science:

• Biotechnology
• Immunology
• Materials Science

Background:

• Active immunotherapies offer an alternative to manufactured antibodies for treating autoimmune diseases.
• Generating therapeutic antibody responses without adverse T cell-mediated autoimmune reactions is a key challenge.

Purpose of the Study:

• To design and evaluate synthetic peptide nanofibers as a platform for active immunotherapy against TNF-mediated inflammation.
• To assess the ability of these nanofibers to induce protective antibody responses against autologous TNF while controlling T cell responses.

Main Methods:

• Synthetic peptide nanofibers were designed to self-assemble and incorporate specific epitopes.
• Mice were immunized with these unadjuvanted peptide nanofibers to assess antibody and T cell responses.
• Therapeutic efficacy was evaluated in a lipopolysaccharide-induced acute inflammation model.
• Immunocompetence was assessed by challenging mice with Listeria monocytogenes.

Main Results:

• Unadjuvanted peptide nanofibers successfully broke B cell tolerance and induced anti-TNF antibody responses in mice.
• The anti-TNF antibody response was tunable by adjusting epitope content, and T cell responses were directed towards non-autoreactive epitopes.
• Immunization with peptide nanofibers demonstrated therapeutic effects in a lethal acute inflammation model.
• These nanofibers did not impair the ability to clear Listeria monocytogenes infections, indicating preserved immune function.

Conclusions:

• Self-assembling synthetic peptide nanofibers represent a promising platform for active immunotherapies targeting autologous molecules.
• This approach allows for the generation of tunable, protective antibody responses while minimizing autoimmune risks.
• The findings suggest a potential new strategy for treating inflammatory diseases like those mediated by TNF.