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首页> 外文期刊>AIDS Research and Human Retroviruses >A Therapeutic SIV DNA Vaccine Elicits T-Cell Immune Responses, but No Sustained Control of Viremia in SIVmac239-Infected Rhesus Macaques
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A Therapeutic SIV DNA Vaccine Elicits T-Cell Immune Responses, but No Sustained Control of Viremia in SIVmac239-Infected Rhesus Macaques

机译：治疗性SIV DNA疫苗引起T细胞免疫反应，但没有持续控制SIVmac239感染的猕猴的病毒血症。

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The immunologic and virologic outcome of therapeutic DNA-vaccines administered during antiretroviral therapy (ART) using electroporation with or without (interleukin) IL-2 treatment was evaluated in the SIVmac239/macaque model. Rhesus macaques inoculated with pathogenic SIVmac239 were treated with ART [(R(-9-(2-phosphonomethoxypropyl) adenine) (PMPA), FTC, Zerit®] from weeks 13 to 41 postinfection (wpi). Group 1 (n = 7) received ART only, groups 2 and 3 (each n = 6) additionally received SIVmac239-derived gp140Env, GagPol, and TatRevNef plasmids by in vivo electroporation at 22, 26, 30, and 34 wpi, and group 3 also IL-2 for 14 days after each vaccination. Endpoints evaluated were viral load, Gag181–189-specific CD8+ T-cell responses in MamuA01+ animals, lymphoproliferative responses, and CD4 T-cell counts. Viremia in all animals dropped below 200 RNA copies/ml during ART. Frequencies of Gag181–189-specific CD8+ T cells prior to ART were detectable in all three groups (1.27–3.01%) and increased significantly (p < 0.01) postvaccination with maximum responses after the fourth immunization (0.2% versus 3.49–7.15%). Gag181–189-specific CD8+ T-cell frequencies increased post-ART cessation in all groups and remained at significantly higher levels (p < 0.001) until the end of the study (75 wpi) in both groups of vaccinated animals. Lymphoproliferative responses were detected against Gag in a limited number of animals after vaccination and post-ART. However, plasma RNA viral loads rebounded after ART termination to similar levels in all three groups, but remained below 105 copies/ml until the end of the study, which could be a late effect of the triple drug therapy
机译：在SIVmac239 /猕猴模型中评估了在抗逆转录病毒治疗（ART）期间使用或不使用（白介素）IL-2进行电穿孔的治疗性DNA疫苗的免疫学和病毒学结果。从感染后第13周到第41周（wpi），用ART [（R（-9-（2-膦酰基甲氧基丙基）腺嘌呤）（PMPA），FTC，Zerit®））处理接种了病原性SIVmac239的恒河猴。仅接受ART治疗的患者，第2和3组（每个n = 6）还分别通过22、26、30和34 wpi的体内电穿孔，分别接受了SIVmac239衍生的gp140Env，GagPol和TatRevNef质粒，第3组也接受了IL-2，分别为14每次接种后的几天，评估的终点是病毒载量，MamuA01 +动物中的Gag181–189特异性CD8 + T细胞反应，淋巴增生反应和CD4 T细胞计数。在ART期间，所有动物的病毒血症均降至200 RNA复制/毫升以下。在所有三组中，ART之前检测到的Gag181–189特异性CD8 + T细胞数量（1.27–3.01％）均显着增加（p <0.01），在第四次免疫后达到最大响应（0.2％对3.49–7.15％）。 Gag181–189特异的CD8 + T细胞频率在所有组中均增加了ART停止后的存活率，并且仍然存在在两组接种动物中，均以显着较高的水平（p <0.001）直至研究结束（75 wpi）。疫苗接种后和ART后，在有限数量的动物中检测到针对Gag的淋巴增生反应。但是，ART终止后，血浆RNA病毒载量在所有三组中均反弹至相似水平，但一直保持低于105拷贝/ ml，直到研究结束，这可能是三联药物治疗的晚期作用

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