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.
Human Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College London, London SW10 9NH, United Kingdom.
Aggeliki
A
Spentzou
Philip
P
Bergin
Dilbinder
D
Gill
Hannah
H
Cheeseman
Ambreen
A
Ashraf
Harry
H
Kaltsidis
Michelle
M
Cashin-Cox
Insiyah
I
Anjarwalla
Alan
A
Steel
Christopher
C
Higgs
Anton
A
Pozniak
Alicja
A
Piechocka-Trocha
Johnson
J
Wong
Omu
O
Anzala
Etienne
E
Karita
Len
L
Dally
Frances
F
Gotch
Bruce
B
Walker
Jill
J
Gilmour
Peter
P
Hayes
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