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Dendritic Cell Therapeutic Vaccine Helps Immune Cells Control HIV Replication

A therapeutic vaccine made from dendritic cells primed with heat-inactivated HIV stimulated immune cells to mount a response against the virus without it infecting and killing them, according to a study described in the January 2, 2013, issue of Science Translational Medicine.

Many HIV vaccine candidates are intended to prevent initial HIV infection, but therapeutic vaccines are designed to inhibit viral activity after infection, with the aim of halting disease progression and potentially allowing people to reduce or stop their antiretroviral therapy (ART).

Felipe Garcia from the University of Barcelona and fellow investigators with the DCV2/MANON07-ORVACS Study Group looked at the safety, tolerability, and immunogenicity (ability to elicit an immune response) of a therapeutic vaccine using autologous monocyte-derived dendritic cells (DCs) pulsed with heat-inactivated whole HIV.

A press release issued by the journal explained the process: "When a microorganism like HIV invades the body, cells called phagocytes chop up the virus and break it into small fragments. Some of these pieces find their way into the membranes of DCs. The DCs then present the pieces of HIV to lymphocytes, white blood cells that then launch a specific immune response against the virus. The problem is that DCs can also carry a part of the infectious virus on their outer membrane. Consequently, the white blood cells can get infected and die instead of developing an immune response."

The study included 36 HIV positive participants with CD4 T-cell counts above 450 cells/mm³. All were on combination ART at study entry. They were randomly assigned (2:1) to receive 3 immunizations using their own DCs either "pulsed" with heat-disabled HIV or unaltered.

Results

• Vaccination using the pulsed DCs was found to be feasible, safe, and well-tolerated.
• The vaccine was able to stimulate an immune response against HIV and "shifted the virus/host balance" in favor of the host.
• At week 12 after ART interruption, 55% of people in the pulsed vaccine group saw their viral load set-point decrease by at least 10-fold or 90%, compared with just 9% in the control group.
• At week 24, these proportions dropped to 35% and 0%, respectively.
• By week 48, only about 15% in the pulsed vaccine group still had viral suppression.
• The significant decrease in viral load seen in recipients of the pulsed vaccine was associated with a consistent increase in HIV-specific T-cell responses.
• The reported adverse events were lymph node enlargement, injection site redness, and flu-like symptoms.

"These data suggest that HIV-1-specific immune responses elicited by therapeutic DC vaccines could significantly change plasma viral load set-point after [combination] ART interruption in chronic HIV-1-infected patients treated in early stages," the study authors concluded. "This proof of concept supports further investigation of new candidates and/or new optimized strategies of vaccination with the final objective of obtaining a functional cure as an alternative to [combination] ART for life."

The study findings "open the possibility that a therapeutic vaccine could be used as a strategy to obtain a functional cure," Garcia commented.

1/15/13

Reference

F Garcia, N Climent, AC Guardo, et al. A Dendritic Cell-Based Vaccine Elicits T Cell Responses Associated with Control of HIV-1 Replication. Science Translational Medicine 5(166):166ra2. January 2, 2013.

Other Source

AAAS. Early Vaccine Boosts Immune Response to HIV. Science Translational Medicine press package for January 2, 2013.