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一种基于DNA/痘苗病毒安卡拉的肯尼亚人类免疫缺陷病毒候选疫苗在恒河猴中诱导多特异性T细胞反应。

A DNA/MVA-based candidate human immunodeficiency virus vaccine for Kenya induces multi-specific T cell responses in rhesus macaques.

作者信息

Wee Edmund G-T, Patel Sandip, McMichael Andrew J, Hanke Tomáš

机构信息

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK1.

出版信息

J Gen Virol. 2002 Jan;83(Pt 1):75-80. doi: 10.1099/0022-1317-83-1-75.

Abstract

The minimum requirement for candidate human immunodeficiency virus (HIV) vaccines to enter clinical evaluation in humans should be their demonstrable immunogenicity in non-human primates: induction of antibodies neutralizing primary HIV isolates or elicitation of broad T cell-mediated immune responses. Here, we showed in rhesus macaques that the very same vaccines that had entered clinical trials in Oxford and Nairobi, plasmid pTHr.HIVA DNA and recombinant modified vaccinia virus Ankara MVA.HIVA in a prime-boost protocol (Hanke & McMichael, Nature Medicine 6, 951-955, 2000), induced cellular immune responses specific for multiple HIV-derived epitopes. This was demonstrated by using the intracellular cytokine staining and ELISPOT assays detecting interferon-gamma and pools of peptides employed in the clinical studies. These results have both boosted our expectations for the performance of these vaccines in humans and increased our confidence about the choice of these assays as the primary readouts in the on-going human trials.

摘要

候选人类免疫缺陷病毒(HIV)疫苗进入人体临床评估的最低要求应该是其在非人灵长类动物中可证明的免疫原性:诱导中和原发性HIV分离株的抗体或引发广泛的T细胞介导的免疫反应。在此,我们在恒河猴中表明,在牛津和内罗毕进入临床试验的相同疫苗,即采用初免-加强方案的质粒pTHr.HIVA DNA和重组改良安卡拉痘苗病毒MVA.HIVA(Hanke & McMichael,《自然医学》6,951 - 955,2000),诱导了针对多种HIV衍生表位的细胞免疫反应。这通过使用细胞内细胞因子染色和ELISPOT检测法得以证明,这些检测法用于检测干扰素-γ以及临床研究中使用的肽池。这些结果既增强了我们对这些疫苗在人体中表现的期望,也增加了我们对选择这些检测法作为正在进行的人体试验主要读数的信心。

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