Treatment of Inflammatory Bowel Disease using phosphorylcholine-presenting nanofibers engaging natural antibody responses

• Published in: Nature biomedical engineering Vol. 8; no. 5; pp. 628 - 649
• Main Authors: Curvino, Elizabeth J., Roe, Emily F., Freire Haddad, Helena, Anderson, Alexa R., Woodruff, Mia E., Votaw, Nicole L., Segura, Tatiana, Hale, Laura P., Collier, Joel H.
• Format: Journal Article
• Language: English
• Published: 27-11-2023
• ISSN: 2157-846X
• DOI: 10.1038/s41551-023-01139-6

Inflammatory bowel disease (IBD) is a chronic disease that lacks a long-lasting and broadly effective therapy. Preexisting natural antibodies targeting the small molecule epitope phosphorylcholine (PC) have shown inherent benefits against infections and inflammation. Here, we present a PC-presenting immunotherapy using supramolecular peptide nanofibers. Conjugating PC epitopes to nanofiber-forming peptide Q11 (PC
M
-Q11) resulted in therapeutic anti-PC antibody production in part through B1a cells. To enhance PC
M
-Q11’s therapeutic efficiency, we adjusted PC multivalency, incorporated exogenous T-cell epitopes, and included CpG adjuvant. In mouse models of colitis induced by dextran sodium sulfate (DSS), PC
M
-Q11 elicited sustained production of anti-PC antibodies, altering the microbiome diversity and ameliorating colitis in both therapeutic and prophylactic models. Our findings suggest that nanomaterials can induce production of therapeutic antibodies for lessening disease severity. This approach holds promise as a durable therapy for overcoming the challenges associated with IBD.