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 HIV -1 isolates. The assay uses relatively simple autologous cell culture and enzyme-linked immunosorbent assay (ELlSA), 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-I replication in vitro was demonstrated in antiretroviral therapy-naive HIV -l-infected subjects with controlled viral replication in vivo but not in viremic subjects. The observed HIV-I inhibition is reversed by blockade of MHC I and physical separation of effector CD8+ and target CD4+ T cells by transwell chambers. An HIV-I vaccine candidate, consisting of adenovirus (Ad) serotype 35 vectors tested in a phase I clinical trial, induced CD8+ T cells that efficiently inhibited HIV -1. 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. 2
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:577536 |
| Date | January 2012 |
| Creators | Spentzou, Aggeliki |
| Publisher | University of London |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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