The kinetics of specific immune responses in rhesus monkeys inoculated with live recombinant BCG expressing SIV Gag, Pol, Env, and Nef proteins.

The kinetics of specific immune responses in rhesus monkeys inoculated with live recombinant BCG expressing SIV Gag, Pol, Env, and Nef proteins.
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DOI:
10.1006/viro.1999.0131
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发表时间:
2000-03
期刊:
影响因子:
3.7
通讯作者:
N. J. Leung;A. Aldovini;R. Young;M. Jarvis;J. M. Smith;D. Meyer;D. Anderson;M. P. Carlos;M. Gardner;J. Torres
N. J. Leung;A. Aldovini;R. Young;M. Jarvis;J. M. Smith;D. Meyer;D. Anderson;M. P. Carlos;M. Gardner;J. Torres
中科院分区:
医学3区
文献类型:
--
作者:
N. J. Leung;A. Aldovini;R. Young;M. Jarvis;J. M. Smith;D. Meyer;D. Anderson;M. P. Carlos;M. Gardner;J. Torres

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研制有效预防或治疗艾滋病毒-1的疫苗是防治艾滋病的一个重要目标。有效的病毒清除和抑制扩散到靶器官主要取决于细胞免疫反应。因此,针对HIV-1的疫苗应该引起病毒特异性的细胞毒性淋巴细胞(CTL)反应,从而在病毒生命周期的细胞相关阶段消灭病毒。疫苗还应能够在粘膜表面产生免疫,这是主要的传播途径。表达病毒蛋白的重组卡介苗(BCG)具有安全性和在细胞内持续存在的能力,可诱导持久免疫并刺激细胞免疫反应,因此是一种极好的候选疫苗。口服卡介苗可在粘膜表面诱导hiv特异性免疫。表达猴免疫缺陷病毒(SIV) Gag、Pol、Env和Nef蛋白的四种重组BCG构建体在恒河猴体内进行了免疫原性测试。单次同时接种所有四种重组病毒可诱导siv特异性IgA和IgG抗体,并产生细胞免疫反应,包括CTL和辅助T细胞增殖。结果表明,BCG重组载体可诱导对SIV主要蛋白的伴随体液和细胞免疫应答。
Development of an effective preventive or therapeutic vaccine against HIV-1 is an important goal in the fight against AIDS. Effective virus clearance and inhibition of spread to target organs depends principally on the cellular immune response. Therefore, a vaccine against HIV-1 should elicit virus-specific cytotoxic lymphocyte (CTL) responses to eliminate the virus during the cell-associated stages of its life cycle. The vaccine should also be capable of inducing immunity at the mucosal surfaces, the primary route of transmission. Recombinant Bacille Calmette-Guérin (BCG) expressing viral proteins offers an excellent candidate vaccine in view of its safety and ability to persist intracellularly, resulting in the induction of long-lasting immunity and stimulation of the cellular immune response. BCG can be administered orally to induce HIV-specific immunity at the mucosal surfaces. The immunogenicity of four recombinant BCG constructs expressing simian immunodeficiency virus (SIV) Gag, Pol, Env, and Nef proteins was tested in rhesus macaques. A single simultaneous inoculation of all four recombinants elicited SIV-specific IgA and IgG antibody, and cellular immune responses, including CTL and helper T cell proliferation. Our results demonstrate that BCG recombinant vectors can induce concomitant humoral and cellular immune responses to the major proteins of SIV.