Viral Inhibition Assay: A CD8 T Cell Neutralization Assay for Use in Clinical Trials of HIV-1 Vaccine Candidates

被引:66
作者
Spentzou, Aggeliki [1 ]
Bergin, Philip [1 ]
Gill, Dilbinder [1 ]
Cheeseman, Hannah [1 ]
Ashraf, Ambreen [1 ]
Kaltsidis, Harry [1 ]
Cashin-Cox, Michelle [1 ]
Anjarwalla, Insiyah [1 ]
Steel, Alan [2 ]
Higgs, Christopher [2 ]
Pozniak, Anton [2 ]
Piechocka-Trocha, Alicja [3 ]
Wong, Johnson [4 ]
Anzala, Omu [6 ]
Karita, Etienne [7 ]
Dally, Len [5 ]
Gotch, Frances [1 ]
Walker, Bruce [3 ]
Gilmour, Jill [1 ]
Hayes, Peter [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Human Immunol Lab, Int AIDS Vaccine Initiat, London, England
[2] Chelsea & Westminster Hosp, London, England
[3] MIT & Harvard, Ragon Inst MGH, Boston, MA USA
[4] Massachusetts Gen Hosp, Boston, MA 02114 USA
[5] EMMES Corp, Rockville, MD USA
[6] Univ Nairobi, Kenya AIDS Vaccine Initiat, Nairobi, Kenya
[7] Projet San Francisco, Kigali, Rwanda
来源
JOURNAL OF INFECTIOUS DISEASES | 2010年 / 201卷 / 05期
关键词
IMMUNODEFICIENCY-VIRUS TYPE-1; IMMUNOGENICITY EVALUATION; UNINFECTED INDIVIDUALS; LYMPHOCYTE ACTIVITY; PHASE-1; SAFETY; INFECTED CELLS; REPLICATION; RESPONSES; IMMUNITY; ESCAPE;
D O I
10.1086/650492
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We have characterized an assay measuring CD8 T cell-mediated inhibition of human immunodeficiency virus (HIV) type 1 replication, demonstrating specificity and reproducibility and employing a panel of primary HIV-1 isolates. The assay uses relatively simple autologous cell culture and enzyme-linked immunosorbent assay, avoids generation of T cell clones, and can be performed with <2 million peripheral blood mononuclear cells. Efficient CD8 T cell-mediated cross-clade inhibition of HIV-1 replication in vitro was demonstrated in antiretroviral therapy-naive HIV-1-infected subjects with controlled viral replication in vivo but not in viremic subjects. An HIV-1 vaccine candidate, consisting of DNA and recombinant adenovirus 5 vectors tested in a phase I clinical trial, induced CD8 T cells that efficiently inhibited HIV-1 in a HLA-I-dependent manner. Assessment of direct antiviral T cell function by this assay provides additional information to guide vaccine design and the prioritizing of candidates for further clinical trials.
引用
收藏
页码:720 / 729
页数:10
相关论文
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