Journal
FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.1029029
Keywords
HIV; CD8 T-cells; viral inhibition; infection; T-cell response; transmitted founder; infectious molecular clones
Categories
Funding
- Bill and Melinda Gates Foundation
- Ministry of Foreign Affairs of Denmark
- Irish Aid
- World Bank
- Ministry of Foreign Affairs of the Netherlands
- Norwegian Agency for Development Cooperation
- United Kingdom Department for International Development
- US Agency for International Development
- National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health [681137]
- Ministry of Finance of Japan
- European Union [681032]
- [R01 AI51231]
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This study describes a functional viral inhibition assay to evaluate the CD8 T-cell-mediated inhibition of HIV-1 replication. The assay was successfully established across multiple clinical research centers and showed reproducibility. This method provides a tool for designing HIV-1 vaccine candidates and evaluating vaccine-induced T-cell immune responses in clinical trials.
IntroductionImmunological 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. MethodsThe 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. Results & discussionCD4 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.
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