Horner A A, Datta S K, Takabayashi K, Belyakov I M, Hayashi T, Cinman N, Nguyen M D, Van Uden J H, Berzofsky J A, Richman D D, Raz E
Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
J Immunol. 2001 Aug 1;167(3):1584-91. doi: 10.4049/jimmunol.167.3.1584.
Immunostimulatory DNA sequences (ISS, also known as CpG motifs) are pathogen-associated molecular patterns that are potent stimulators of innate immunity. We tested the ability of ISS to act as an immunostimulatory pathogen-associated molecular pattern in a model HIV vaccine using gp120 envelope protein as the Ag. Mice immunized with gp120 and ISS, or a gp120:ISS conjugate, developed gp120-specific immune responses which included: 1) Ab production; 2) a Th1-biased cytokine response; 3) the secretion of beta-chemokines, which are known to inhibit the use of the CCR5 coreceptor by HIV; 4) CTL activity; 5) mucosal immune responses; and 6) CD8 T cell responses that were independent of CD4 T cell help. Based on these results, ISS-based immunization holds promise for the development of an effective preventive and therapeutic HIV vaccine.
免疫刺激DNA序列(ISS,也称为CpG基序)是与病原体相关的分子模式,是先天免疫的有效刺激物。我们在一个以gp120包膜蛋白为抗原的HIV疫苗模型中测试了ISS作为免疫刺激病原体相关分子模式的能力。用gp120和ISS或gp120:ISS偶联物免疫的小鼠产生了gp120特异性免疫反应,包括:1)抗体产生;2)以Th1为主的细胞因子反应;3)β趋化因子的分泌,已知其可抑制HIV对CCR5共受体的利用;4)CTL活性;5)黏膜免疫反应;6)独立于CD4 T细胞辅助的CD8 T细胞反应。基于这些结果,基于ISS的免疫接种有望开发出有效的预防性和治疗性HIV疫苗。