Biotin Functionalized Self-Assembled Peptide Nanofiber as an Adjuvant for Immunomodulatory Response.

Demircan, Muhammed Burak; Tohumeken, Sehmus; Gunduz, Nuray; Khalily, Mohammad Aref; Tekinay, Turgay; Guler, Mustafa O; Tekinay, Ayse B

The design and development of novel adjuvants, which enhance, accelerate, and prolong the immune responses triggered by antigens, hold great importance for targeting infectious diseases and cancer. Here, we designed a biotinylated peptide amphiphile (Biotin-PA) nanofiber, which serves as a noncovalent binding location for antigens. We showed that presenting the antigens on synthetic Biotin-PA nanofibers generated a higher immune response than the free antigens delivered with a CpG ODN (TLR9 agonist) adjuvant. Antigen attached Biotin-PA nanofibers triggered splenocytes to produce high levels of cytokines (IFN-γ, IL-12, TNF-α, and IL-6) and to exhibit a superior cross-presentation of the antigen. Both Biotin-PA nanofibers and CpG ODN induce a Th-1-biased IgG subclass response; however, delivering the antigen with Biotin-PA nanofibers induced significantly greater production of total IgG and subclasses of IgG compared to delivering the antigen with CpG ODN. Contrary to CpG ODN, Biotin-PA nanofibers also enhanced antigen-specific splenocyte proliferation and increased the proportion of the antigen-specific CD8(+) T cells. Given their biodegradability and biocompatibility, Biotin-PA nanofibers have a significant potential in immunoengineering applications as a biomaterial for the delivery of a diverse set of antigens derived from intracellular pathogens, emerging viral diseases such as COVID-19, or cancer cells to induce humoral and cellular immune responses against the antigens. This article is protected by copyright. All rights reserved.