Immunization of cats against feline immunodeficiency virus (FIV) infection by using minimalistic immunogenic defined gene expression vector vaccines expressing FIV gp140 alone or with feline interleukin-12 (IL-12), IL-16, or a CpG motif

Immunization of cats against feline immunodeficiency virus (FIV) infection by using minimalistic immunogenic defined gene expression vector vaccines expressing FIV gp140 alone or with feline interleukin-12 (IL-12), IL-16, or a CpG motif
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DOI:
10.1128/jvi.74.22.10447-10457.2000
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发表时间:
2000-11-01
影响因子:
5.4
通讯作者:
Lutz, H
Lutz, H
中科院分区:
医学2区
文献类型:
--
作者:
Leutenegger, CM;Boretti, FS;Lutz, H

文献摘要

被引文献

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在0、3和6周时,用含有猫免疫缺陷病毒(FIV)gp 140、FIV gp 140和猫白细胞介素-12(IL-12)、FIV gp 140和猫IL-16或FIV gp 140和CpG基序的基因的最小免疫原性确定基因表达载体(MIDGE)疫苗免疫四组猫,每组包含四只动物。将MIDGE包被在金珠上并用基因枪皮内注射。第五组四只猫以相同的方式免疫,但使用空白金珠。在最后一次免疫后4周,所有猫被攻击暴露于强毒FIV,并监测感染过程。用FIV gp 140基因单独免疫或用空白金颗粒免疫的两组猫在感染后4周就变成高度病毒血症和血清转化。相反,用FIV gp 140和猫IL-12联合免疫的四只猫中有三只未能变成病毒血症或血清阳性,如别处所示(F. S.博雷蒂角M.洛伊特内格角Mislin等人,AIDS 14:1749-1757,2000)。在这里,我们显示了IL-12作为佐剂对病毒RNA和DNA载量以及细胞因子谱的影响。此外,用gp 140和IL-16或用gp 140和CpG免疫的两组猫的病毒血症大大减少。保护弱相关的细胞毒性T淋巴细胞活性和增加细胞因子转录的IL-12,γ干扰素,IL-10的外周血单核细胞在攻毒后阶段。这项研究扩展了IL-12的数据,并提供了CpG基序和IL-16在FIV猫模型中用作佐剂的新结果。
Four groups of cats, each containing four animals, were immunized at 0, 3, and 6 weeks with minimalistic immunogenic defined gene expression vector (MIDGE) vaccines containing the gene(s) for feline immunodeficiency virus (FIV) gp140, FIV gp140 and feline interleukin-12 (IL-12), FIV gp140 and feline IL-16, or FIV gp140 and a CpG motif. MIDGEs were coated onto gold beads and injected intradermally with a gene gun. A fifth group of four cats were immunized in an identical manner but with blank gold beads. All cats were challenge exposed to virulent FIV 4 weeks following the final immunization, and the course of infection was monitored. The two groups of cats immunized with the FIV gp140 gene alone or with blank gold particles became highly viremic and seroconverted as early as 4 weeks after infection. In contrast, three of four cats immunized with FIV gp140 in combination with feline IL-12 failed to become viremic or seropositive, as has been shown elsewhere (F. S. Boretti, C. M. Leutenegger, C. Mislin, et al., AIDS 14:1749-1757, 2000). Here we show the effect of IL-12 when used as an adjuvant on the viral RNA and DNA load and on the cytokine profile. In addition, the two groups of cats immunized either with gp140 and IL-16 or with gp140 and the CpG had greatly reduced viremia. Protection correlated weakly with cytotoxic T-lymphocyte activity and increased cytokine transcription of IL-12, gamma interferon, and IL-10 by peripheral blood mononuclear cells in the postchallenge period. This study extends the data on IL-12 and provides new results on CpG motifs and IL-16 used as adjuvants in the FIV cat model.