Viral inhibition assay: a CD8 T cell neutralization assay for use in clinical trials of HIV-1 vaccine candidates.
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.
Spentzou
Aggeliki
A
Human Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College London, London SW10 9NH, United Kingdom.
Bergin
Philip
P
Gill
Dilbinder
D
Cheeseman
Hannah
H
Ashraf
Ambreen
A
Kaltsidis
Harry
H
Cashin-Cox
Michelle
M
Anjarwalla
Insiyah
I
Steel
Alan
A
Higgs
Christopher
C
Pozniak
Anton
A
Piechocka-Trocha
Alicja
A
Wong
Johnson
J
Anzala
Omu
O
Karita
Etienne
E
Dally
Len
L
Gotch
Frances
F
Walker
Bruce
B
Gilmour
Jill
J
Hayes
Peter
P
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000260:Adenoviruses, Human / Q000235:genetics; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005822:Genetic Vectors; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014779:Virus Replication / Q000276:immunology
D016915:AIDS Vaccines