Viral Inhibition Assay: A CD8 T Cell Neutralization Assay for Use in Clinical Trials of Human Immunodeficiency Virus-1 Vaccine Candidates
Year of Publication
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
J Infect Dis
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
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.