Viral Inhibition Assay: A CD8 T Cell Neutralization Assay for Use in Clinical Trials of Human Immunodeficiency Virus-1 Vaccine Candidates
03/2010
Journal Article
Authors:
Spentzou, A.;
Bergin, P.;
Gill, D.;
Cheeseman, H.;
Ashraf, A.;
Kaltsidis, H.;
Cashin-Cox, M.;
Anjarwalla, I.;
Steele, A.;
Higgs, C.;
Pozniak, A.;
Piechocka-Trocha, A.;
Wong, J.;
Anzala, O.;
Karita, E.;
Dally, L.;
Gotch, F.;
Walker, B.;
Gilmour, J.;
Hayes, P.
Secondary:
J Infect Dis
Volume:
201
Pagination:
720-729
URL:
http://www.ncbi.nlm.nih.gov/pubmed/20132004
Keywords:
Adenoviruses; Adult; Aged; AIDS Vaccines; CD8-Positive T-Lymphocytes; Enzyme-Linked Immunosorbent Assay; Female; Genetic Vectors; HIV-1; Male; Middle Aged; Neutralization Tests; Research Non-U.S. Gov; Research USGov Non-PHS; sensitivity
Abstract:
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.
