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

页码：720 / 729

页数：10