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

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 F F Y (Gel-gffy) that can evoke potent humoral and cellular immune respo...

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Bibliographic Details
Published in:Biomaterials science 2022-06, Vol.10 (12), p.3092-3098
Main Authors: Zhang, Yiming, Hu, Zhiwen, Li, Xinxin, Ding, Yinghao, Zhang, Zhenghao, Zhang, Xiangyang, Zheng, Wenting, Yang, Zhimou
Format: Article
Language:English
Subjects:
Adjuvants
Amino acids
Bone marrow
Dichroism
Glycine
Hydrogels
Immune system
Ovalbumin
Peptides
Phenylalanine
Self-assembly
Sol-gel processes
Tyrosine
Vaccines
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Summary: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 F F 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 . 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.
ISSN:2047-4830
2047-4849
DOI:10.1039/d2bm00263a