title: mRNA-based dendritic cell vaccination induces potent antiviral T-cell responses in HIV-1-infected patients.
abstract: BACKGROUND
  In an effort to raise protective antiviral immunity, dendritic cell immunotherapy was evaluated in six adults infected with human immunodeficiency virus (HIV)-1 and stable under highly active antiretroviral therapy (HAART).
  
  
  METHODS
  Autologous monocyte-derived dendritic cells electroporated with mRNA encoding Gag and a chimeric Tat-Rev-Nef protein were administered, whereas patients remained on HAART. Feasibility, safety, immunogenicity and antiviral responses were investigated.
  
  
  RESULTS
  Dendritic cell vaccine preparation and administration were successful in all patients and only mild adverse events were seen. There was a significant increase post-dendritic cell as compared to pre-dendritic cell vaccination in magnitude and breadth of HIV-1-specific interferon (IFN)-γ response, in particular to Gag, and in T-cell proliferation. Breadth of IFN-γ response and T-cell proliferation were both correlated with CD4(+) and CD8(+) polyfunctional T-cell responses. Importantly, dendritic cell 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-γ response.
  
  
  CONCLUSIONS
  Therapeutic immunization with dendritic cells 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 dendritic cell vaccination in the treatment of HIV-1. The incomplete nature of the response in some patients helped to identify potential targets for future improvement, that is increasing antigenic spectrum and enhancing T-cell response.
authors.affiliation: Department of Biomedical Sciences, Division of Microbiology, Virology Unit, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Van Gulck
authors.forename: Erika
authors.initials: E
authors.lastname: Vlieghe
authors.forename: Marc
authors.initials: M
authors.lastname: Vekemans
authors.forename: Viggo F I
authors.initials: VF
authors.lastname: Van Tendeloo
authors.forename: Ann
authors.initials: A
authors.lastname: Van De Velde
authors.forename: Evelien
authors.initials: E
authors.lastname: Smits
authors.forename: Sébastien
authors.initials: S
authors.lastname: Anguille
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cools
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
authors.forename: Liesbet
authors.initials: L
authors.lastname: Mertens
authors.forename: Winni
authors.initials: W
authors.lastname: De Haes
authors.forename: Johnsson
authors.initials: J
authors.lastname: Wong
authors.forename: Eric
authors.initials: E
authors.lastname: Florence
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
authors.forename: Zwi N
authors.initials: ZN
authors.lastname: Berneman
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D018274:Electroporation; D005240:Feasibility Studies; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D054298:Human Immunodeficiency Virus Proteins / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000276:immunology*; D012367:RNA, Viral / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000998:Antiviral Agents; D054298:Human Immunodeficiency Virus Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; D054321:rev Gene Products, Human Immunodeficiency Virus; C514860:rev protein, Human Immunodeficiency Virus-1; D054322:tat Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma