Several Vaccine Trials Affected By Halt Of Merck's HIV Vaccine Trial

Several vaccine trials are being postponed or modified following the halt of Merck's experimental HIV vaccine trial, the Philadelphia Inquirer reports (Stark, Philadelphia Inquirer, 11/16). Merck in September announced that it had ended the Phase II trial, which began in late 2004 and involved HIV-negative volunteers, after the experimental vaccine failed to prevent HIV infection in participants or prove effective in delaying the progression of the virus to AIDS.

New data recently suggested that the vaccine was ineffective among some trial participants with a pre-existing immunity to a common cold virus and that the vaccine might have increased their susceptibility to HIV infection. The Merck vaccine was made from a weakened version of a common cold virus that served as a mode for providing three synthetically produced genes from HIV, known as gag, pol and nef.

After several days of discussions at an HIV Vaccine Trials Network conference last week in Seattle of Merck's trial, leaders of the trial on Monday decided to notify all of the trial's 3,000 participants whether they were given the vaccine or a placebo (Kaiser Daily HIV/AIDS Report, 11/14).

According to the Inquirer, other trials have been affected by Merck's trial because the experimental vaccines have a similar structure to Merck's vaccine. Trial participants now must be warned about the potential risks highlighted in the Merck trail if they participate in experiments that use a cold-virus carrier similar to Merck's product, Anthony Fauci, director of the National Institute of Allergy and Infectious Disease, said.

Gary Nabel, director of NIH's Vaccine Research Center, was scheduled to launch the PAVE 100 HIV vaccine trial early next year, but it recently was postponed until at least mid-2008. The PAVE vaccine uses three shots of DNA followed by a cold-virus booster shot, which has different components than the Merck vaccine. Nabel said he plans to modify the study by testing the vaccine only on people with limited exposure to colds and by increasing monitoring of patients.

Hildegund Ertl -- an immunologist at the Wistar Institute who is preparing to test an experimental HIV vaccine that uses a chimpanzee cold virus -- said the Merck trial also likely will affect her study, which is due to start in a year. "The bar will be raised," she said, adding that she hopes the chimp-based cold virus will not cause complications that the human cold virus might be causing (Philadelphia Inquirer, 11/16). Vaccines Using Some Viruses Require Further Testing, Study Says
Ertl and colleagues on Thursday in the Journal of Clinical Investigation reported that experimental HIV vaccines that typically use harmless viruses called adeno-associated viruses might damage the immune system by exhausting important cells, Reuters reports.

According to the group, AAV vaccines when tested in mice directly interfered with immune cells called CD8 T-cells, which are T-cells that a vaccine is supposed to stimulate to fight HIV. "The immune cells become exhausted," Ertl said, adding, "It is simply a defense mechanism of T-cells -- if there is too much antigen for too long a time they simply turn themselves off." The researchers said AAV vaccines should not be tested on people until more studies are conducted. Ertl said it is unclear whether her findings contributed to the developments in Merck's trial, which used an adenovirus.

Fauci said the study should be taken "with a very heavy dose of caution." He added that adenoviruses and adeno-associated viruses are very different microbes, despite the similarity of their names. "We may be dealing with apples and oranges," he said.

Pat Fast of the International AIDS Vaccine Initiative said the group has stopped testing AAV vaccines. "While we find the AAV study by Dr. Ertl and her group ... very interesting and we'll consider whether it can inform our future studies, their study was conducted in mice and there are fundamental differences between mice and humans in their respective immune responses, particularly with regard to the immune response against HIV," Fast said in a statement (Fox, Reuters, 11/15).

The study is available online (.pdf).

Reprinted with kind permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation. © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.