Plasmid-Encoded Interleukin-15 Receptor α Enhances Specific Immune Responses Induced by a DNA Vaccine In Vivo
Plasmid-Encoded Interleukin-15 Receptor α Enhances Specific Immune Responses Induced by a DNA Vaccine In Vivo
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DOI：
10.1089/hum.2009.025
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发表时间：
2009-10-01
影响因子：
4.2
通讯作者：
Weiner, David B.
中科院分区：
文献类型：
--
作者：
Kraynyak, Kimberly A.;Kutzler, Michele A.;Weiner, David B.
质粒编码的DNA疫苗似乎是一种安全有效的递送抗原的方法;然而，此类疫苗的免疫原性通常是次优的。包括白细胞介素（IL）-12、RANTES、粒细胞-巨噬细胞集落刺激因子、IL-15等的细胞因子佐剂已用于增强针对DNA疫苗的免疫应答。特别地，IL-15结合至独特的高亲和力受体IL-15 R α;被反式呈递至表达共同β γ链的CD 8（+）T细胞;并且已显示在抗原特异性CD 8（+）T细胞的产生、维持和增殖中起作用。在这项研究中，我们采取了独特的方法，在HIV-1疫苗策略中同时使用细胞因子及其受体作为佐剂。为了研究IL-15 R α表达，生成了独特的单克隆抗体（KK 1.23）以确认体外受体表达。IL-15和IL-15 R α质粒与HIV-1抗原性质粒在小鼠中的共免疫增强了抗原特异性免疫应答，比单独的IL-15免疫佐剂高2倍。此外，质粒编码的IL-15 R α在不存在IL-15的情况下增强免疫应答，表明其作为新型佐剂的作用。此外，pIL-15 R α增强细胞免疫应答，但不增强体液免疫应答，如通过抗原特异性IgG抗体所测量的。这是第一份描述IL-15 R α本身可以通过增强抗原特异性T细胞应答而充当佐剂的报告。独特的是，pIL-15和pIL-15 R α佐剂组合，而不是单独的受体α链，可能是有用的，作为一种策略，在DNA疫苗中产生和维持记忆CD 8（+）T细胞。
Plasmid-encoded DNA vaccines appear to be a safe and effective method for delivering antigen; however, the immunogenicity of such vaccines is often suboptimal. Cytokine adjuvants including interleukin (IL)-12, RANTES, granulocyte-macrophage colony-stimulating factor, IL-15, and others have been used to augment the immune response against DNA vaccines. In particular, IL-15 binds to a unique high-affinity receptor, IL-15R alpha; is trans-presented to CD8(+) T cells expressing the common beta gamma chain; and has been shown to play a role in the generation, maintenance, and proliferation of antigen-specific CD8(+) T cells. In this study, we took the unique approach of using both a cytokine and its receptor as an adjuvant in an HIV-1 vaccine strategy. To study IL-15R alpha expression, a unique monoclonal antibody (KK1.23) was generated to confirm receptor expression in vitro. Coimmunization of IL-15 and IL-15R alpha plasmids with HIV-1 antigenic plasmids in mice enhanced the antigen-specific immune response 2-fold over IL-15 immunoadjuvant alone. Furthermore, plasmid-encoded IL-15R alpha augments immune responses in the absence of IL-15, suggesting its role as a novel adjuvant. Moreover, pIL-15R alpha enhanced the cellular, but not the humoral, immune response as measured by antigen-specific IgG antibody. This is the first report describing that IL-15R alpha itself can act as an adjuvant by enhancing an antigen-specific T cell response. Uniquely, pIL-15 and pIL-15R alpha adjuvants combined, but not the receptor a chain alone, may be useful as a strategy for generating and maintaining memory CD8(+) T cells in a DNA vaccine.