4.5 Article

Amino acid sequence determines the adjuvant potency of a d-tetra-peptide hydrogel

期刊

BIOMATERIALS SCIENCE
卷 10, 期 12, 页码 3092-3098

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ROYAL SOC CHEMISTRY
DOI: 10.1039/d2bm00263a

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资金

  1. National Nature Science Foundation of China [21875116, 31961143004, 82101933]
  2. CAMS Innovation Fund for Medical Sciences [2021-I2M-1-041]

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The amino acid sequence of the peptide determines the adjuvant potency of Gel-gffy. The position and number of aromatic amino acids play a crucial role in the immunostimulatory activity of Gel-gffy. These findings provide valuable insights into designing peptide hydrogels as vaccine adjuvants.
The development of novel vaccine adjuvants is essential for the production of modern vaccines against infectious agents and cancer. We recently reported a supramolecular hydrogel of a self-assembling D-tetra-peptide named Nap-G(D)F(D)F(D)Y (Gel-gffy) that can evoke potent humoral and cellular immune responses; however, the determinants of its immunostimulatory properties were not characterized. In this study, we show that the amino acid sequence of the peptide determines the adjuvant potency of Gel-gffy. We designed and synthesized five Gel-gffy variants (Sol-gfgy, Sol-ggfy, Gel-gffg, Gel-gfyf, and Gel-gyff) by substituting the phenylalanine and tyrosine to glycine or changing the position of the tyrosine in the parent d-tetra-peptide. First, we characterized their gelation properties, nanomorphology, and secondary structure using transmission electron microscopy and circular dichroism; next, we examined their immunostimulatory properties. Gel-gfyf, Gel-gyff and Gel-gffy markedly upregulated maturation marker expression on bone marrow-derived dendritic cells. Moreover, the Gel-gfyf-, Gel-gyff- or Gel-gffy-encapsulated ovalbumin (OVA) vaccine induced robust humoral and cellular immune response in vivo. Notably, Gel-gffy had the strongest immunostimulatory activity. Our findings demonstrate that both the position and number of aromatic amino acids are crucial in determining the adjuvant potency of Gel-gffy, thus providing a valuable insight into designing peptide hydrogels as vaccine adjuvants.

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