Plasmid DNA vaccines are effective in the absence of IFNgamma.
Plasmid DNA vaccines are effective in the absence of IFNgamma.
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质粒 DNA 疫苗在没有 IFNgamma 的情况下也有效。
DOI：
10.1006/viro.1999.9957
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Whitton,JL
中科院分区：
文献类型：
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作者：
Hassett,DE;Zhang,J;Whitton,JL
肌内注射细菌来源的质粒 DNA 会导致针对质粒编码抗原的体液和细胞免疫反应的发展。细菌 DNA 中的免疫刺激 CpG 序列被认为可以通过刺激先天免疫系统细胞分泌促炎细胞因子（例如干扰素 γ (IFNγ)）来增强这一过程。尽管质粒 DNA 内的 CpG 元件诱导 IFNγ 已在体外和最近在体内得到记录，并且与表达 IFNγ 的质粒共免疫已被证明可以增强 DNA 免疫诱导的免疫反应，但尚不清楚 IFNγ 是否是成功 DNA 免疫所必需的。为了解决这个问题，我们比较了接种表达沙粒病毒淋巴细胞脉络膜脑膜炎病毒（LCMV）核蛋白基因的质粒（pCMVNP）的野生型和IFNγ缺陷小鼠的体液和细胞免疫反应。 IFNγ 阳性 (BALB/c) 和 IFNγ 阴性 (GKO) 小鼠通过产生抗原特异性 CD8+T 细胞对 DNA 疫苗接种做出反应，这些细胞可通过细胞内细胞因子染色在体外直接检测到，占疫苗接种者所有 CD8+T 细胞的 0.7-2.5%。即使没有 IFNγ，DNA 疫苗也能诱导病毒特异性细胞毒性 T 淋巴细胞 (CTL)。两种小鼠品系的 DNA 疫苗接种也与 LCMV 攻击后病毒滴度显着降低有关，这表明，至少在其他免疫效应机制存在的情况下，通过 DNA 免疫诱导保护性抗病毒免疫不需要 IFNγ。尽管 GKO 小鼠确实表现出 IgG2a:IgG1 比例显着降低，但 GKO 和 BALB/c 疫苗接种者的抗病毒 IgG 水平没有观察到定量差异，这与之前记录的同种型转换为 IgG2a 时对 IFNγ 的要求一致。免疫的 BALB/c 小鼠产生相似水平的 IgG1 和 IgG2a，表明对 pCMVNP 肌内免疫的混合 Th1/Th2 反应。这些结果表明，细菌来源的质粒DNA诱导的IFNγ不会影响抗体反应的强度，并且对于DNA诱导的CTL的诱导或短期维持来说不是必需的。然而，IFNγ 对于 IgG2a 抗体的形成是必需的，而 IgG2a 抗体对于防御某些病原体可能至关重要。
Intramuscular injection of bacterially derived plasmid DNA results in the development of both humoral and cellular immune responses against plasmid-encoded antigens. Immunostimulatory CpG sequences within bacterial DNA are thought to enhance this process by stimulating the secretion of proinflammatory cytokines such as interferon γ (IFNγ) by cells of the innate immune system. Although IFNγ induction by CpG elements within plasmid DNA has been documented in vitro and more recently in vivo, and coimmunization with plasmids expressing IFNγ has been shown to enhance DNA-immunization-induced immune responses, it is unclear if IFNγ is necessary for successful DNA immunization. To address this issue, we compared humoral and cellular immune responses in wild-type and IFNγ-deficient mice vaccinated with a plasmid (pCMVNP) expressing the nucleoprotein gene from the arenavirus lymphocytic choriomeningitis virus (LCMV). IFNγ-positive (BALB/c) and IFNγ-negative (GKO) mice responded to DNA vaccination by the development of antigen-specific CD8+T cells, which were detectable directly ex vivo by intracellular cytokine staining and comprised 0.7–2.5% of all CD8+T cells in the vaccinee. DNA vaccines also induced virus-specific cytotoxic T lymphocytes (CTL), even in the absence of IFNγ. DNA vaccination of both mouse strains also was associated with a significant reduction in viral titers after LCMV challenge, indicating that, at least in the presence of other immune effector mechanisms, IFNγ is not required for induction of protective anti-viral immunity by DNA immunization. No quantitative differences were observed in antiviral IgG levels among GKO and BALB/c vaccinees, although GKO mice did exhibit a significant reduction of the IgG2a:IgG1 ratio, in agreement with the previously documented requirement for IFNγ in isotype switching to IgG2a. Immunized BALB/c mice produced similar levels of both IgG1 and IgG2a, indicating a mixed Th1/Th2 response to intramuscular immunization with pCMVNP. These results show that IFNγ induction by bacterially derived plasmid DNA does not contribute to the magnitude of the antibody response and is not required for the induction or short-term maintenance of DNA-induced CTL. However, IFNγ is necessary for the development of IgG2a antibodies that may be crucial for protection against some pathogens.