title: Therapeutic immunization with human immunodeficiency virus type 1 (HIV-1) peptide-loaded dendritic cells is safe and induces immunogenicity in HIV-1-infected individuals.
abstract: Treatments for human immunodeficiency virus type 1 (HIV-1)-positive individuals that augment HIV-1 suppression and have potential for achieving long-term control of HIV-1 viremia in the absence of antiretroviral therapy (ART) are urgently needed. We therefore conducted a phase I, clinical safety trial of a dendritic cell (DC)-based vaccination strategy as immunotherapy for HIV-1-positive individuals on ART. We studied 18 HIV-1-positive subjects on ART who underwent leukapheresis to obtain peripheral blood mononuclear cells for DC generation from monocytes cultured with cytokines. Mature DC were pulsed with three HIV-1 HLA*A0201 Gag, Env, and Pol peptides and one influenza A virus matrix protein peptide. The vaccine was administered to donors randomized to receive two vaccinations, either intravenously or subcutaneously. The primary end points were safety and tolerability of two doses of peptide-DC vaccine (3 million versus 10 million). Secondary end points included gamma interferon (IFN-gamma) enzyme-linked immunospot assay responses and clinical correlates of an immune response to vaccination. Autologous DC-peptide vaccine was safe, well tolerated, and feasible for use in all participants. Adverse events were rare. Although the trial was not powered to assess an immunologic response, a significantly increased frequency of HIV-1 peptide-specific IFN-gamma-positive cells was observed 2 weeks following the second vaccine, with three individuals responding to all four peptides. DC vaccination was safe, was feasible, and showed promise of immunogenicity in ART-treated, HIV-1-positive individuals. Additional studies of DC immunization strategies for HIV-1 infection are warranted.
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Connolly
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Whiteside
authors.forename: Cara
authors.initials: C
authors.lastname: Wilson
authors.forename: Venkatswarlu
authors.initials: V
authors.lastname: Kondragunta
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Riddler
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects* / Q000379:methods*; D009980:Influenza A virus / Q000276:immunology; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D007937:Leukapheresis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014764:Viral Proteins / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D000939:Epitopes; D014764:Viral Proteins; D007371:Interferon-gamma