1. Assessment of a diverse panel of transmitted/founder HIV-1 infectious molecular clones in a luciferase based CD8 T-cell mediated viral inhibition assay
- Author
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Natalia, Fernandez, Peter, Hayes, Julia, Makinde, Jonathan, Hare, Deborah, King, Rui, Xu, Ola, Rehawi, Allison T, Mezzell, Laban, Kato, Susan, Mugaba, Jennifer, Serwanga, James, Chemweno, Eunice, Nduati, Matt A, Price, Faith, Osier, Christina, Ochsenbauer, Ling, Yue, Eric, Hunter, and Jill, Gilmour
- Subjects
HIV-1 ,Humans ,HIV Infections ,CD8-Positive T-Lymphocytes ,Luciferases ,Clone Cells - Abstract
Immunological protection against human immunodeficiency virus-1 (HIV-1) infection is likely to require both humoral and cell-mediated immune responses, the latter involving cytotoxic CD8 T-cells. Characterisation of CD8 T-cell mediated direct anti-viral activity would provide understanding of potential correlates of immune protection and identification of critical epitopes associated with HIV-1 control.The present report describes a functional viral inhibition assay (VIA) to assess CD8 T-cell-mediated inhibition of replication of a large and diverse panel of 45 HIV-1 infectious molecular clones (IMC) engineered with aCD4 and CD8 T-cell lines were established from subjects vaccinated with a candidate HIV-1 vaccine and provided standard positive controls for both assay quality control and facilitating training and technology transfer. The assay was successfully established across 3 clinical research centres in Kenya, Uganda and the United Kingdom and shown to be reproducible. This IMC-LucR VIA enables characterisation of functional CD8 T-cell responses providing a tool for rational T-cell immunogen design of HIV-1 vaccine candidates and evaluation of vaccine-induced T-cell responses in HIV-1 clinical trials.
- Published
- 2022