4.8 Article

Assessment of a diverse panel of transmitted/founder HIV-1 infectious molecular clones in a luciferase based CD8 T-cell mediated viral inhibition assay

期刊

FRONTIERS IN IMMUNOLOGY
卷 13, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.1029029

关键词

HIV; CD8 T-cells; viral inhibition; infection; T-cell response; transmitted founder; infectious molecular clones

资金

  1. Bill and Melinda Gates Foundation
  2. Ministry of Foreign Affairs of Denmark
  3. Irish Aid
  4. World Bank
  5. Ministry of Foreign Affairs of the Netherlands
  6. Norwegian Agency for Development Cooperation
  7. United Kingdom Department for International Development
  8. US Agency for International Development
  9. National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health [681137]
  10. Ministry of Finance of Japan
  11. European Union [681032]
  12. [R01 AI51231]

向作者/读者索取更多资源

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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