利用小鼠模型评价含有5＇-GTCGTT-3＇特征序列的人CpG寡脱氧核苷酸的免疫刺激活性

为了寻找合适的动物模型来评价人CpG寡脱氧核苷酸（CpG-ODN）的活性，研究了CpG2006等含有5＇-GTCGTT-3＇特征序列的人CpG-ODN对小鼠的免疫刺激活性。在体外它们能够促进小鼠脾淋巴细胞转化，促进B细胞分泌IgM，但不能诱生高水平的IFN-γ。研究了CpG2006等序列在体内作为疫苗佐剂对HBsAg免疫效果的影响，发现（1）人CpG-ODN能够明显提高抗-HBs抗体水平，并逆转Al（OH）

Evaluation of Immunostimulatory Activities of Human CpG-ODN Containing 5'-GTCGTT-3' Motif in Murine Model

While bacterial DNA and synthetic oligodeoxynucleotides(ODN)containing unmethylated CpG dinucleotides with specific flanking sequences are well described activators of murine immune cells, CpG-ODN for activating human immune responses remains unclear. Recently Krieg et al. and our group have identified that the sequences with 5'-GTCGTT-3' motif acted as immunostimulatory CpG-ODN for human B lymphocytes, and also we found they cross-activated with murine immune cells. In the present study, we evaluated their activities in a murine model. In vitro, human CpG-ODN induced murine splenocyte transformation and production of IgM, but no IFN-γ. The in vivo adjuvanticity of human CpG-ODN for recombinant HBsAg was examined in mice. And the data showed that (1)human CpG-ODN induced a strong Th1 response with predominant IgG2a isotype, and (2)the immune response could be anchored at Th1 response when primed with human CpG-ODN, and (3)boosting with human CpG-ODN partially reversed the Th2 response induced by alum during priming, and (4)one dose of HBsAg with human CpG-ODN as adjuvant elicited a stronger humoral response (Th1 biased)than two doses of conventional vaccine with alum (Th2 biased). These studies demonstrated that mice may be used as an animal model for the evaluation of the activities of some human CpG-ODN, and it also indicated that CpG-ODN containing 5'-GTCGTT-3' motif is a candidate adjuvant for human vaccines.