肽
佐剂
氨基酸
卵清蛋白
化学
肽序列
圆二色性
生物化学
表位
免疫系统
分子生物学
抗体
生物
免疫学
基因
作者
Yiming Zhang,Zhi-Wen Hu,Xinxin Li,Yinghao Ding,Zhenghao Zhang,Xiangyang Zhang,Wenting Zheng,Zhimou Yang
出处
期刊:Biomaterials Science
[The Royal Society of Chemistry]
日期:2022-01-01
卷期号:10 (12): 3092-3098
被引量:7
摘要
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-GDFDFDY (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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