Immunostimulatory DNA-based vaccines induce cytotoxic lymphocyte activity by a T-helper cell-independent mechanism
Immunostimulatory DNA-based vaccines induce cytotoxic lymphocyte activity by a T-helper cell-independent mechanism
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DOI：
10.1038/75365
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发表时间：
2000-05-01
影响因子：
46.9
通讯作者：
Raz, E
中科院分区：
文献类型：
--
作者：
Cho, HJ;Takabayashi, K;Raz, E
免疫刺激性DNA序列（ISS）在确定的基序内含有未甲基化的CpG二核苷酸。已显示用基于ISS的疫苗免疫可诱导高抗原特异性细胞毒性淋巴细胞（CTL）活性和T（h）1偏向性免疫应答。我们已经开发了一种新的ISS疫苗组成的卵清蛋白（OVA）的化学结合ISS-寡脱氧核苷酸（ODN）。蛋白质-ISS偶联物（PIC）比其他基于ISS的疫苗更有效地引发CTL活性和T（h）1偏向性免疫。基于ISS-ODN的疫苗的细胞毒性淋巴细胞活化在CD 4（-/-）和MHC II类基因缺陷动物中得以保留。此外，PIC以CD 8（+）细胞依赖性方式提供针对表达OVA的肿瘤细胞的致死负荷的保护。这些结果表明，PIC通过两种独特的机制：T辅助细胞非依赖性CTL激活和促进外源性抗原呈递MHCI类。该技术可能在癌症治疗和刺激艾滋病和慢性免疫抑制中的宿主防御方面具有临床应用。
Immunostimulatory DNA sequences (ISS) contain unmethylated CpG dinucleotides within a defined motif. Immunization with ISS-based vaccines has been shown to induce high antigen-specific cytotoxic lymphocyte (CTL) activity and a T(h)1-biased immune response. We have developed a novel ISS-based vaccine composed of ovalbumin (OVA) chemically conjugated to ISS-oligodeoxynucleotide (ODN). Protein-ISS conjugate (PIC) is more potent in priming CTL activity and T(h)1-biased immunity than other ISS-based vaccines. Cytotoxic lymphocyte activation by ISS-ODN-based vaccines is preserved in both CD4(-/-) and MHC class II-/- gene-deficient animals. Furthermore, PIC provides protection against a lethal burden of OVA-expressing tumor cells in a CD8(+) cell-dependent manner. These results demonstrate that PIC acts through two unique mechanisms: T-helper-independent activation of CTL and facilitation of exogenous antigen presentation on MHC class I. This technology may have clinical applications in cancer therapy and in stimulating host defense in AIDS and chronic immunosuppression.