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Assessment of a diverse panel of transmitted/founder HIV-1 infectious molecular clones in a luciferase based CD8 T-cell mediated viral inhibition assay.
- Source :
-
Frontiers in immunology [Front Immunol] 2022 Dec 01; Vol. 13, pp. 1029029. Date of Electronic Publication: 2022 Dec 01 (Print Publication: 2022). - Publication Year :
- 2022
-
Abstract
- Introduction: 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.<br />Methods: 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 a Renilla reniformis luciferase reporter gene (LucR), referred to as IMC-LucR. HIV-1 IMC replication in CD4 T-cells and CD8 T-cell mediated inhibition was characterised in both ART naive subjects living with HIV-1 covering a broad human leukocyte antigen (HLA) distribution and compared with uninfected subjects.<br />Results & Discussion: CD4 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.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2022 Fernandez, Hayes, Makinde, Hare, King, Xu, Rehawi, Mezzell, Kato, Mugaba, Serwanga, Chemweno, Nduati, Price, Osier, Ochsenbauer, Yue, Hunter, Gilmour and The IAVI protocol C investigators.)
- Subjects :
- Humans
CD8-Positive T-Lymphocytes
Luciferases
Clone Cells
HIV-1
HIV Infections
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 13
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 36532063
- Full Text :
- https://doi.org/10.3389/fimmu.2022.1029029