Viral inhibition assay: a CD8 T cell neutralization assay for use in clinical trials of HIV-1 vaccine candidates.

Publication Type
Journal Article
Year of Publication
Spentzou, Aggeliki; Bergin, Philip; Gill, Dilbinder; Cheeseman, Hannah; Ashraf, Ambreen; Kaltsidis, Harry; Cashin-Cox, Michelle; Anjarwalla, Insiyah; Steel, Alan; Higgs, Christopher; Pozniak, Anton; Piechocka-Trocha, Alicja; Wong, Johnson; Anzala, Omu; Karita, Etienne; Dally, Len; Gotch, Frances; Walker, Bruce; Gilmour, Jill; Hayes, Peter
J Infect Dis
Date Published
2010 Mar
Adenoviruses, Human; Adult; Aged; AIDS Vaccines; CD8-Positive T-Lymphocytes; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Female; Genetic Vectors; HIV-1; Humans; Male; Middle Aged; Neutralization Tests; Reproducibility of Results; Sensitivity and Specificity; Virus Replication

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.