Abstract：
Immune stimulants (adjuvants) enhance immune system recognition to provide an effective and individualized immune response when delivered with an antigen. Synthetic cyclic deca-peptides, co-administered with a toll-like receptor targeting lipopeptide, have shown self-adjuvant properties, dramatically boosting the immune response in a murine model as a subunit peptide-based vaccine containing group A Streptococcus peptide antigens.Here, we designed a novel peptide and lipid adjuvant system for the delivery of group A Streptococcus peptide antigen and a T helper peptide epitope. Following linear peptide synthesis on 2-chlorotrityl chloride resin, the linear peptide was cleaved and head-to-tail cyclized in solution. The selective arrangement of amino acids in the deca-peptide allowed for selective conjugation of lipids and/or peptide antigens following cyclisation. Using both solution-phase peptide chemistry and copper-catalyzed azide-alkyne cycloaddition reaction were covalently (and selectively) ligated lipid and/or peptide antigens onto the cyclic deca-peptide core. Subcutaneous administration of the vaccine design to mice resulted in the generation of a large number of serum immunoglobulin (Ig) G antibodies.
摘要：
当与抗原一起递送时,免疫刺激剂(佐剂)增强免疫系统识别以提供有效和个性化的免疫应答。合成环状deca肽，与Toll样受体靶向脂肽共同给药，显示了自佐剂特性，作为包含A组链球菌肽抗原的基于亚基肽的疫苗，在小鼠模型中显着增强了免疫反应。这里,我们设计了一种新型的肽和脂质佐剂系统，用于递送A组链球菌肽抗原和T辅助肽表位。在2-氯三苯甲基氯树脂上合成线性肽后，线性肽被裂解并在溶液中头尾环化。十肽中氨基酸的选择性排列允许脂质和/或肽抗原在环化后选择性缀合。使用液相肽化学和铜催化的叠氮化物-炔环加成反应将脂质和/或肽抗原共价（和选择性）连接到环状十肽核心上。对小鼠皮下施用疫苗设计导致产生大量血清免疫球蛋白(Ig)G抗体。
