Olive C, Schulze K, Sun H Kuo, Ebensen T, Horváth A, Toth I, Guzman C A
Cooperative Research Centre for Vaccine Technology, Division of Infectious Diseases and Immunology, The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia.
Vaccine. 2007 Feb 26;25(10):1789-97. doi: 10.1016/j.vaccine.2006.11.031. Epub 2006 Nov 30.
We investigated the efficacy of a synthetic Streptococcus pyogenes vaccine targeting two virulence factors using the Lipid Core Peptide (LCP) delivery system. BALB/c mice were immunised intranasally with LCPs containing peptides encompassing T-cell and B-cell epitopes of the conserved C-repeat region of the M protein (J8) or the fibronectin-binding repeats region (FNBR) of SfbI, or a combination formulation containing peptides representing both antigens. LCPs were co-administered with the TLR2/6 agonist MALP-2 as mucosal adjuvant. Humoral and cellular immune responses stimulated at systemic and mucosal levels were strongest in mice immunised with the dual antigen formulation. Mice were completely protected following a respiratory challenge with a lethal dose of a heterologous S. pyogenes strain, whereas there was 70% and 90% survival in mice immunised with LCP-J8 and LCP-FNBR, respectively. This is the first report demonstrating the elicitation of better protective immunity by a dual antigen component S. pyogenes vaccine.
我们使用脂质核心肽(LCP)递送系统研究了一种针对两种毒力因子的化脓性链球菌合成疫苗的疗效。将BALB/c小鼠经鼻免疫含有包含M蛋白保守C重复区域(J8)的T细胞和B细胞表位的肽或SfbI的纤连蛋白结合重复区域(FNBR)的肽的LCP,或含有代表两种抗原的肽的联合制剂。LCP与TLR2/6激动剂MALP-2作为粘膜佐剂共同给药。在用双抗原制剂免疫的小鼠中,在全身和粘膜水平刺激的体液和细胞免疫反应最强。在用致死剂量的异源化脓性链球菌菌株进行呼吸道攻击后,小鼠得到完全保护,而在用LCP-J8和LCP-FNBR免疫的小鼠中,存活率分别为70%和90%。这是第一份证明双抗原成分化脓性链球菌疫苗能引发更好的保护性免疫的报告。