Agger Else Marie, Rosenkrands Ida, Olsen Anja Weinreich, Hatch Graham, Williams Ann, Kritsch Constantia, Lingnau Karen, von Gabain Alexander, Andersen Claire Swetman, Korsholm Karen Smith, Andersen Peter
Department of Infectious Disease Immunology, Statens Serum Institut, Adjuvant Research, 5 Artillerivej, DK-2300 Copenhagen S, Denmark.
Vaccine. 2006 Jun 29;24(26):5452-60. doi: 10.1016/j.vaccine.2006.03.072. Epub 2006 Apr 17.
In this study, we evaluated the potential of a novel synthetic adjuvant designated IC31 for the ability to augment the immune response and protective efficacy of the well-known mycobacterial vaccine antigen, Ag85B-ESAT-6. The IC31 adjuvant, consisting of a vehicle based on the cationic peptide KLKL(5)KLK and the immunostimulatory oligodeoxynucleotide ODN1a signalling through the TLR9 receptor, was found to promote highly efficient Th1 responses. The combination of Ag85B-ESAT-6 and IC31 exhibited significant levels of protection in the mouse aerosol challenge model of tuberculosis and a detailed analysis of the immune response generated revealed the induction of CD4 T cells giving rise to high levels of IFN-gamma secretion. Furthermore, the combination of Ag85B-ESAT-6/IC31 was found to confer efficient protection in the guinea pig aerosol model of tuberculosis infection and is at present moving towards clinical testing.
在本研究中，我们评估了一种名为IC31的新型合成佐剂增强著名的分枝杆菌疫苗抗原Ag85B - ESAT - 6免疫应答和保护效力的潜力。IC31佐剂由基于阳离子肽KLKL(5)KLK的载体和通过TLR9受体发出信号的免疫刺激寡脱氧核苷酸ODN1a组成，被发现可促进高效的Th1应答。Ag85B - ESAT - 6与IC31的组合在小鼠气溶胶攻击肺结核模型中表现出显著的保护水平，对所产生免疫应答的详细分析显示，诱导产生了能分泌高水平γ干扰素的CD4 T细胞。此外，Ag85B - ESAT - 6/IC31组合在豚鼠气溶胶结核感染模型中被发现具有有效的保护作用，目前正迈向临床试验阶段。
