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

Journal Contribution - Journal Article

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.
Journal: AIDS
ISSN: 0269-9370
Issue: 4
Volume: 26
Pages: F1-F12
Publication year:2012
Keywords: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
  • Scopus Id: 84857045791
  • PubMed Id: 22156965