Supramolecular Peptide Self-Assemblies Facilitate Oral Immunization.

Area of Science:

• Biotechnology
• Immunology
• Materials Science

Background:

• Oral immunization offers direct access to the gastrointestinal (GI) tract for disease prevention and treatment.
• Significant challenges for oral vaccines include proteolytic degradation and mucus barriers within the GI tract.

Purpose of the Study:

• To develop a peptide nanofiber platform for effective oral immunization against peptide and small molecule epitopes.
• To engineer nanofibers resistant to proteases and capable of penetrating mucus barriers in the GI tract.

Main Methods:

• Utilized a modular, self-assembling peptide nanofiber platform.
• Synthesized d-amino acid nanofibers for protease resistance and l-amino acid nanofibers with proline, alanine, and serine (PAS) for enhanced muco-penetration.
• Administered PASylated nanofibers with a mucosal adjuvant in mouse models for oral immunization.

Main Results:

• d-amino acid nanofibers demonstrated in vitro protease resistance.
• PASylated l-amino acid nanofibers enhanced muco-penetration and GI tract transport.
• Oral immunization with PASylated nanofibers elicited local and systemic immune responses to a peptide epitope.
• Demonstrated therapeutic and prophylactic effectiveness against colitis using small molecule epitope immunization.

Conclusions:

• Supramolecular peptide self-assemblies show potential as oral vaccines.
• The developed nanofiber platform effectively overcomes GI tract barriers for oral immunization.
• This approach holds promise for developing novel immunotherapies for GI diseases.