By Michael Smith, North American Correspondent, MedPage Today
Published: November 13, 2010
Reviewed by Barry S. Zingman, MD; Professor of Clinical Medicine, Albert Einstein College of Medicine, Bronx, NY.
A therapeutic HIV vaccine appears to reverse some of the immune dysfunction caused by the virus, researchers reported.
According to preliminary data from a randomized phase II trial, a vaccine against the HIV protein Tat was both safe and immunogenic, according to Barbara Ensoli, MD, PhD, of the National AIDS Center of the Istituto Superiore di Sanità in Rome, and colleagues.
But in patients with fully suppressed HIV replication, the vaccine also appeared to improve a range of markers of immune function, Ensoli and colleagues reported online in PLoS One.
Even when highly active anti-retroviral therapy (HAART) slows HIV replication, there is often enough growth to cause continued immune activation in patients, Ensoli and colleagues noted, and immune homeostasis is impaired.
The Tat protein is essential for HIV replication, so Ensoli and colleagues are testing several doses and vaccination schedules of a recombinant protein in a phase II randomized trial, designed to determine immunogenicity and safety.
But a secondary goal is to see what effect the vaccine has on immune parameters, including such things as the number of B cells, CD4-positive T cells, and CD8-positive T cells.
For this analysis -- described as "ad hoc and exploratory" -- Ensoli and colleagues analyzed results from 87 volunteers and compared them with patients taking part in a separate, prospective observational trial that is examining the effect of naturally-occurring Tat immunity.
The 87 volunteers in the trial had no antibodies to Tat, but had undetectable HIV on a range of HAART regimens. They were given either 7.5 or 30 micrograms intradermally, either three or five times.
Overall, Ensoli and her colleagues found, 79% of the volunteers responded to the vaccine by producing antibodies to Tat.
Although 59% of the volunteers had at least one adverse event, they were mostly the usual side effects associated with HIV infection, the researchers said. Of those that were linked to the Tat vaccine most were local, related to the injection, and mild.
The researchers reported seven serious adverse events, but only one -- a severe case of disarthria and paresthesia -- was regarded as possibly related to the drug. It resolved after the vaccine was stopped.
The researchers also found that responders had:
• Significant increases in interleukin-2, interferon-gamma, and interleukin-4, as well as Tat-specific CD4 and CD8 T cells
• Improvements in the in vitro viability of peripheral blood mononuclear cells, which is lessened in HIV infection, that continued to increase for up to 48 weeks and were significant at that point at P<0.0001
• Increases in the number of CD4 T cells, ranging on average from 48 to 69 cells/mL of blood, depending on dose
• Increases in the number of B cells that ranged on average from 25 to 66 cells/mL of blood
• An increased proportion of CD4 T cells and B cells, but a decrease in the proportion of CD8 T cells and natural killer cells -- a marker of immune activation
The responses, in general, were better with the larger dose, the researchers reported.
The results, Ensoli said in a statement, "suggest that therapeutic vaccination with the Tat vaccine, combined with HAART, can significantly improve the recovery of the immune system in patients with HIV."
The study was supported by the Italian health ministry.
The researchers said they had no disclosures.
Primary source: PLoS One
Source reference:
Ensoli B, et al. "Therapeutic Immunization with HIV-1 Tat Reduces Immune Activation and Loss of Regulatory T-Cells and Improves Immune Function in Subjects on HAART." PLoS ONE 5(11): e13540.
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