Leutenegger C M, Boretti F S, Mislin C N, Flynn J N, Schroff M, Habel A, Junghans C, Koenig-Merediz S A, Sigrist B, Aubert A, Pedersen N C, Wittig B, Lutz H
Clinical Laboratory, Department of Internal Veterinary Medicine, University of Zurich, 8057 Zurich, Switzerland.
J Virol. 2000 Nov;74(22):10447-57. doi: 10.1128/jvi.74.22.10447-10457.2000.
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.
将四组猫（每组四只）在第0、3和6周用含有猫免疫缺陷病毒（FIV）gp140基因、FIV gp140和猫白细胞介素-12（IL-12）基因、FIV gp140和猫IL-16基因或FIV gp140和CpG基序的简约免疫原性定义基因表达载体（MIDGE）疫苗进行免疫。将MIDGE包被在金珠上，并用基因枪进行皮内注射。第五组四只猫以相同方式用空白金珠进行免疫。所有猫在最后一次免疫后4周接受强毒FIV攻击暴露，并监测感染过程。单独用FIV gp140基因或用空白金颗粒免疫的两组猫在感染后4周就出现了高病毒血症并发生血清转化。相比之下，用FIV gp140与猫IL-12联合免疫的四只猫中有三只未出现病毒血症或血清阳性，这在其他地方已有报道（F.S.博雷蒂、C.M.洛伊滕内格、C.米斯林等人，《艾滋病》14:1749 - 1757，2000年）。在此我们展示了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gp140和IL-16或用gp140和CpG免疫的两组猫的病毒血症大大降低。保护作用与细胞毒性T淋巴细胞活性以及攻击后外周血单个核细胞中IL-12、γ干扰素和IL-10细胞因子转录增加之间的相关性较弱。本研究扩展了关于IL-12的数据，并提供了在FIV猫模型中用作佐剂的CpG基序和IL-16的新结果。
