Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science, Nankai University Affiliated Eye Hospital, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, P. R. China.
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
Biomater Sci. 2022 Jun 14;10(12):3092-3098. doi: 10.1039/d2bm00263a.
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-GFFY (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.
新型疫苗佐剂的开发对于生产针对传染病和癌症的现代疫苗至关重要。我们最近报道了一种自组装 D-四肽的超分子水凝胶，名为 Nap-GFFY（Gel-gffy），它可以引发强烈的体液和细胞免疫反应；然而，其免疫刺激特性的决定因素尚未得到表征。在这项研究中，我们表明肽的氨基酸序列决定了 Gel-gffy 的佐剂效力。我们通过将苯丙氨酸和酪氨酸替换为甘氨酸或改变母体 D-四肽中酪氨酸的位置来设计和合成了五种 Gel-gffy 变体（Sol-gfgy、Sol-ggfy、Gel-gffg、Gel-gfyf 和 Gel-gyff）。首先，我们使用透射电子显微镜和圆二色性研究了它们的胶凝特性、纳米形态和二级结构；接下来，我们研究了它们的免疫刺激特性。Gel-gfyf、Gel-gyff 和 Gel-gffy 显着上调了骨髓来源树突状细胞上的成熟标志物表达。此外，Gel-gfyf、Gel-gyff 或 Gel-gffy 包封的卵清蛋白（OVA）疫苗诱导了强大的体液和细胞免疫反应。值得注意的是，Gel-gffy 具有最强的免疫刺激活性。我们的研究结果表明，芳香族氨基酸的位置和数量对于确定 Gel-gffy 的佐剂效力至关重要，从而为设计作为疫苗佐剂的肽水凝胶提供了有价值的见解。
