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

Rajesh T. Gandhi, Douglas S. Kwon, Eric A. Macklin, Janet R. Shopis, Anna P. McLean, Nicole McBrine, Theresa Flynn, Lauren Peter, Amy Sbrolla, Daniel E. Kaufmann, Filippos Porichis, Bruce D. Walker, Nina Bhardwaj, Dan H. Barouch, Daniel G. Kavanagh

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

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 interferongamma 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. Conclusion: Immunization with DCs transfected with mRNA encoding HIV-1 Gag and Nef did not induce significant interferongamma 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.

Original languageEnglish
Pages (from-to)246-253
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume71
Issue number3
DOIs
StatePublished - 2016

Keywords

  • HIV-1
  • Immunization
  • Randomized controlled trial
  • Therapeutic vaccine
  • mRNA-transfected dendritic cell

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