Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid
Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid
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DOI：
10.1073/pnas.0709198104
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发表时间：
2007-11-20
影响因子：
11.1
通讯作者：
Weiner, David B.
中科院分区：
文献类型：
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作者：
Boyer, Jean D.;Robinson, Tara M.;Weiner, David B.
在猴/HIV（SHIV）和猕猴模型中评估了重组DNA疫苗诱导的细胞介导的免疫特征。疫苗策略包括单独或与编码猕猴IL-15（pmacIL-15）的优化质粒组合的基于DNA的疫苗的共免疫。我们观察到在接种组中疫苗特异性IFN-γ产生的CD8（+）和CD4（+）效应T细胞的强烈诱导。随后用89.6p激发动物。疫苗组被保护免于持续的感染，IL-15共接种组显示出比单独用DNA疫苗治疗的组更快地控制感染。从与pmacIL-15共接种的组中分离的淋巴细胞比从仅接受SHIV DNA的猕猴中分离的淋巴细胞具有更高的细胞增殖反应。还针对一系列免疫分子研究了淋巴细胞的疫苗抗原活化。虽然IFN-γ的mRNA在抗原刺激后上调，但炎性分子IL-8和MMP-9下调。这些观察到的免疫特征潜在地反映了不同组控制SHIV复制的能力。这项研究表明，与DNA疫苗一起递送的优化IL-15免疫佐剂可以影响非人灵长类动物的细胞免疫特征，并增强对病毒复制的抑制。
The cell-mediated immune profile induced by a recombinant DNA vaccine was assessed in the simian/HIV (SHIV) and macaque model. The vaccine strategy included coimmunization of a DNA-based vaccine alone or in combination with an optimized plasmid encoding macaque IL-15 (pmacIL-15). We observed strong induction of vaccine-specific IFN-gamma-producing CD8(+) and CD4(+) effector T cells in the vaccination groups. Animals were subsequently challenged with 89.6p. The vaccine groups were protected from ongoing infection, and the IL-15 covaccinated group showed a more rapidly controlled infection than the group treated with DNA vaccine alone. Lymphocytes isolated from the group covaccinated with pmacIL-15 had higher cellular proliferative responses than lymphocytes isolated from the macaques that received SHIV DNA alone. Vaccine antigen activation of lymphocytes was also studied for a series of immunological molecules. Although mRNA for IFN-gamma was up-regulated after antigen stimulation, the inflammatory molecules IL-8 and MMP-9 were down-regulated. These observed immune profiles are potentially reflective of the ability of the different groups to control SHIV replication. This study demonstrates that an optimized IL-15 immune adjuvant delivered with a DNA vaccine can impact the cellular immune profile in nonhuman primates and lead to enhanced suppression of viral replication.