mRNA-based dendritic cell vaccination induces potent antiviral T-cell responses in HIV-1-infected patients

E. Van Gulck, E Vlieghe, M Vekemans, VF Van Tendeloo, A Van de Velde, E Smits, S Anguille, N Cools, H Goossens, L Mertens, W De Haes, J Wong, E Florence, G Vanham, ZN Berneman

Research output: Contribution to journalA1: Web of Science-article

Abstract

BACKGROUND: In an effort to raise protective antiviral immunity, dendritic cell (DC) immunotherapy was evaluated in 6 adults infected with human immunodeficiency virus (HIV)-1 and stable under antiretroviral therapy (HAART). DESIGN & METHODS:: Autologous monocyte-derived DC electroporated with mRNA encoding Gag and a chimeric Tat-Rev-Nef protein were administered, while patients remained on HAART. Feasibility, safety, immunogenicity and antiviral responses were investigated. RESULTS: DC vaccine preparation and administration were successful in all patients and only mild adverse events were seen. There was a significant increase post-DC as compared to pre-DC vaccination in magnitude and breadth of HIV-1-specific interferon (IFN)-gamma response, in particular to Gag, and in T-cell proliferation. Breadth of IFN-gamma response and T-cell proliferation were both correlated with CD4+ and CD8+ polyfunctional T-cell responses. Importantly, DC vaccination induced or increased the capacity of autologous CD8+ T-cells to inhibit superinfection of CD4+ T-cells with the vaccine-related IIIB virus and some but not all other HIV-1 strains tested. This HIV-1-inhibitory activity, indicative of improved antiviral response, was correlated with magnitude and breadth of Gag-specific IFN-gamma response. CONCLUSIONS: Therapeutic immunization with DC was safe and successful in raising antiviral cellular immune responses, including effector CD8+ T-cells with virus inhibitory activity. The stimulation of those potent immunological and antiviral effects, which have been associated with control of HIV-1, underscores the potential of DC vaccination in the treatment of HIV-1. The incomplete nature of the response in some patients helped to identify potential targets for future improvement, i.e. increasing antigenic spectrum and enhancing T-cell response.
Original languageEnglish
JournalAIDS
Volume26
Issue number4
Pages (from-to)F1-F12
ISSN0269-9370
DOIs
Publication statusPublished - 2012

Keywords

  • B780-tropical-medicine
  • Viral diseases
  • HIV-1
  • AIDS
  • HAART
  • Antiretrovirals
  • Immunotherapy
  • Vaccination
  • Immunity
  • mRNA
  • Dendritic cells
  • T-cells
  • Gag
  • Tat
  • Evaluation
  • Feasibility
  • Safety
  • Immunogenicity
  • IFN-g
  • CD4-positive-T-lymphocytes
  • CD8-positive-T-lymphocytes

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