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J Infect Dis. 2016 May 1;213(9):1400-9. doi: 10.1093/infdis/jiv582. Epub 2015 Dec 8.

Therapeutic Vaccination With Dendritic Cells Loaded With Autologous HIV Type 1-Infected Apoptotic Cells.

Author information

1
Division of Infectious Diseases, University of Pittsburgh School of Medicine.
2
National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
3
Hillman Cancer Center, University of Pittsburgh Medical Center.
4
Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pennsylvania.

Abstract

BACKGROUND:

We report the results of a phase I/II, open-label, single-arm clinical trial to evaluate the safety and anti-human immunodeficiency virus type 1 (HIV-1) efficacy of an autologous dendritic cell (DC)-based HIV-1 vaccine loaded with autologous HIV-1-infected apoptotic cells.

METHODS:

Antiretroviral therapy (ART)-naive individuals were enrolled, and viremia was suppressed by ART prior to delivery of 4 doses of DC-based vaccine. Participants underwent treatment interruption 6 weeks after the third vaccine dose. The plasma HIV-1 RNA level 12 weeks after treatment interruption was compared to the pre-ART (ie, baseline) level.

RESULTS:

The vaccine was safe and well tolerated but did not prevent viral rebound during treatment interruption. Vaccination resulted in a modest but significant decrease in plasma viremia from the baseline level (from 4.53 log10 copies/mL to 4.27 log10 copies/mL;P= .05). Four of 10 participants had a >0.70 log10 increase in the HIV-1 RNA load in plasma following vaccination, despite continuous ART. Single-molecule sequencing of HIV-1 RNA in plasma before and after vaccination revealed increases in G>A hypermutants in gag and pol after vaccination, which suggests cytolysis of infected cells.

CONCLUSIONS:

A therapeutic HIV-1 vaccine based on DCs loaded with apoptotic bodies was safe and induced T-cell activation and cytolysis, including HIV-1-infected cells, in a subset of study participants.

CLINICAL TRIALS REGISTRATION:

NCT00510497.

KEYWORDS:

HIV-1; apoptotic cell; dendritic cell; residual viremia; therapeutic vaccine

PMID:
26647281
PMCID:
PMC4813736
DOI:
10.1093/infdis/jiv582
[Indexed for MEDLINE]
Free PMC Article

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