title: Immunization of HIV-1-Infected Persons With Autologous Dendritic Cells Transfected With mRNA Encoding HIV-1 Gag and Nef: Results of a Randomized, Placebo-Controlled Clinical Trial.
abstract: BACKGROUND
  HIV-1 eradication may require reactivation of latent virus along with stimulation of HIV-1-specific immune responses to clear infected cells. Immunization with autologous dendritic cells (DCs) transfected with viral mRNA is a promising strategy for eliciting HIV-1-specific immune responses. We performed a randomized controlled clinical trial to evaluate the immunogenicity of this approach in HIV-1-infected persons on antiretroviral therapy.
  
  
  METHODS
  Fifteen participants were randomized 2:1 to receive intradermal immunization with HIV-1 Gag- and Nef-transfected DCs (vaccine) or mock-transfected DCs (placebo) at weeks 0, 2, 6, and 10. All participants also received DCs pulsed with keyhole limpet hemocyanin (KLH) to assess whether responses to a neo-antigen could be induced.
  
  
  RESULTS
  After immunization, there were no differences in interferon-gamma enzyme-linked immunospot responses to HIV-1 Gag or Nef in the vaccine or placebo group. CD4 proliferative responses to KLH increased 2.4-fold (P = 0.026) and CD8 proliferative responses to KLH increased 2.5-fold (P = 0.053) after vaccination. There were increases in CD4 proliferative responses to HIV-1 Gag (2.5-fold vs. baseline, 3.4-fold vs. placebo, P = 0.054) and HIV-1 Nef (2.3-fold vs. baseline, 6.3-fold vs. placebo, P = 0.009) among vaccine recipients, but these responses were short-lived.
  
  
  CONCLUSIONS
  Immunization with DCs transfected with mRNA encoding HIV-1 Gag and Nef did not induce significant interferon-gamma enzyme-linked immunospot responses. There were increases in proliferative responses to HIV-1 antigens and to a neo-antigen, KLH, but the effects were transient. Dendritic cell vaccination should be optimized to elicit stronger and long-lasting immune responses for this strategy to be effective as an HIV-1 therapeutic vaccine.
authors.affiliation: *Massachusetts General Hospital, Division of Infectious Diseases, Boston, MA; †Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA; ‡Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA; §Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) and University of Montreal, Montréal, QC, Canada; ‖Howard Hughes Medical Institute, Chevy Chase, MD; ¶Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; and #Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Rajesh T
authors.initials: RT
authors.lastname: Gandhi
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Kwon
authors.forename: Eric A
authors.initials: EA
authors.lastname: Macklin
authors.forename: Janet R
authors.initials: JR
authors.lastname: Shopis
authors.forename: Anna P
authors.initials: AP
authors.lastname: McLean
authors.forename: Nicole
authors.initials: N
authors.lastname: McBrine
authors.forename: Theresa
authors.initials: T
authors.lastname: Flynn
authors.forename: Lauren
authors.initials: L
authors.lastname: Peter
authors.forename: Amy
authors.initials: A
authors.lastname: Sbrolla
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kaufmann
authors.forename: Filippos
authors.initials: F
authors.lastname: Porichis
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Nina
authors.initials: N
authors.lastname: Bhardwaj
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Kavanagh
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D000328:Adult; D003713:Dendritic Cells / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control / Q000628:therapy*; D006801:Humans; D007114:Immunization; D007271:Injections, Intradermal; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology; D014162:Transfection; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D012333:RNA, Messenger; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1