School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia.
Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
Biomater Sci. 2021 Dec 21;10(1):281-293. doi: 10.1039/d1bm01333e.
Untreated or reoccurring group A (GAS) infection can lead to a number of post-infection complications, including rheumatic heart disease. There is no licenced vaccine for the treatment or prevention of GAS infection. We identified that a cyclic decapeptide plays a significant positive influence on the adjuvant activity of several lipid-antigen mixtures. Here, three synthetic vaccine components were synthesised: (1) J8-PADRE represents the GAS B cell antigen (J8) conjugated to the universal T helper epitope (PADRE); (2) a synthetic toll like receptor 2 (TLR2) ligand based on a C16 alkyl chain lipid moiety; and (3) a cyclic carrier deca-peptide. Previously, through structure-immune activity investigations, it was observed that a physical mixture of these three components had significantly higher IgG immune responses when compared to a fully conjugated vaccine construct. Expanding the scope of this structure-activity investigation, we show that the presence of the cyclic peptide is required for the induction of a strong, balanced Th1/Th2 immune response when compared with lipid and antigen only, and cyclic lipopeptide plus B/T cell antigen physical mixtures.
未经治疗或复发的 A 组链球菌(GAS)感染可导致多种感染后并发症,包括风湿性心脏病。目前尚无针对 GAS 感染的治疗或预防疫苗。我们发现一种环状十肽对几种脂质抗原混合物的佐剂活性有显著的积极影响。在这里,我们合成了三种疫苗成分:(1)J8-PADRE 代表与通用 T 辅助表位(PADRE)偶联的 GAS B 细胞抗原(J8);(2)一种基于 C16 烷基链脂质部分的合成 Toll 样受体 2(TLR2)配体;(3)环状载体十肽。此前,通过结构-免疫活性研究观察到,与完全共轭疫苗构建体相比,这三种成分的物理混合物具有更高的 IgG 免疫反应。在这个结构-活性研究的范围内,我们表明,与仅含有脂质和抗原相比,环状肽的存在对于诱导强烈的、平衡的 Th1/Th2 免疫反应是必需的,并且与环状脂质肽加 B/T 细胞抗原物理混合物也是必需的。
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