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Clinical and Vaccine Immunology, February 2008, p. 284-292, Vol. 15, No. 2
1071-412X/08/$08.00+0     doi:10.1128/CVI.00221-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Therapeutic Immunization with Human Immunodeficiency Virus Type 1 (HIV-1) Peptide-Loaded Dendritic Cells Is Safe and Induces Immunogenicity in HIV-1-Infected Individuals

Departments of Medicine,¹ Pathology,² Center for Clinical Pharmacology, University of Pittsburgh School of Medicine,⁵ Departments of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health,⁶ University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania,³ University of Colorado Health Sciences Center, Denver, Colorado 80262⁴

Received 31 May 2007/ Returned for modification 7 August 2007/ Accepted 9 October 2007

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-) 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--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.

Published ahead of print on 17 October 2007.

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• Huang, X.-L., Fan, Z., Borowski, L., Rinaldo, C. R. (2008). Maturation of dendritic cells for enhanced activation of anti-HIV-1 CD8+ T cell immunity. J. Leukoc. Biol. 83: 1530-1540 [Abstract] [Full Text]