Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination
Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination
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DOI：
10.1126/science.290.5491.486
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发表时间：
2000-10-20
期刊：
影响因子：
56.9
通讯作者：
Letvin, NL
中科院分区：
文献类型：
--
作者：
Barouch, DH;Santra, S;Letvin, NL
随着越来越多的证据表明细胞毒性T淋巴细胞（CTL）在感染个体中抑制人类免疫缺陷病毒-1（HIV-1）复制的重要性，人们正在寻求用原型HIV-1疫苗诱导病毒特异性CTL的策略。在这里，我们报告了疫苗引起的免疫应答对恒河猴致病性SHIV-89.6P攻击的保护作用。通过表达SIVmac 239 Gag和HIV-1 89.6 P Env的DNA疫苗引发免疫应答，通过施用纯化的融合蛋白IL-2/IG或编码IL-2/IG的质粒增强免疫应答，所述融合蛋白由白细胞介素-2（IL-2）和免疫球蛋白G（IgG）的Fc部分组成。在SHIV-89.6P感染后，假疫苗接种的猴子产生了弱的CTL应答、CD 4（+）T细胞的快速损失、无病毒特异性CD 4（+）T细胞应答、高设定点病毒载量、显著的临床疾病进展，并且在攻击后第140天有一半动物死亡。相反，所有接受IL-2/IG增强的DNA疫苗的猴子都被感染，但在攻击后第140天表现出有效的继发性CTL应答、稳定的CD 4（+）T细胞计数、保留的病毒特异性CD 4（+）T细胞应答、低至不可检测的设定点病毒载量，并且没有临床疾病或死亡的证据。
With accumulating evidence indicating the importance of cytotoxic T Lymphocytes (CTLs) in containing human immunodeficiency virus-1 (HIV-1) replication in infected individuals, strategies are being pursued to elicit virus-specific CTLs with prototype HIV-1 vaccines. Here, we report the protective efficacy of vaccine-elicited immune responses against a pathogenic SHIV-89.6P challenge in rhesus monkeys. Immune responses were elicited by DNA vaccines expressing SIVmac239 Gag and HIV-1 89.6P Env, augmented by the administration of the purified fusion protein IL-2/Ig, consisting of interleukin-2 (IL-2) and the Fc portion of immunoglobulin G (IgG), or a plasmid encoding IL-2/Ig. After SHIV-89.6P infection, sham-vaccinated monkeys developed weak CTL responses, rapid Loss of CD4(+) T cells, no virus-specific CD4(+) T cell responses, high setpoint viral loads, significant clinical disease progression, and death in half of the animals by day 140 after challenge. in contrast, all monkeys that received the DNA vaccines augmented with IL-2/Ig were infected, but demonstrated potent secondary CTL responses, stable CD4(+) T cell counts, preserved virus-specific CD4(+) T cell responses, Low to undetectable setpoint viral Loads, and no evidence of clinical disease or mortality by day 140 after challenge.