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

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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 IItrial, which began in late 2004 and involved HIV-negative volunteers,after the experimental vaccine failed to prevent HIV infection inparticipants or prove effective in delaying the progression of thevirus to AIDS.

New data recently suggested that the vaccinewas ineffective among some trial participants with a pre-existingimmunity to a common cold virus and that the vaccine might haveincreased their susceptibility to HIV infection. The Merck vaccine wasmade from a weakened version of a common cold virus that served as amode for providing three synthetically produced genes from HIV, knownas gag, pol and nef.

After several days of discussions at an HIV Vaccine Trials Networkconference last week in Seattle of Merck's trial, leaders of the trialon Monday decided to notify all of the trial's 3,000 participantswhether 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 theexperimental vaccines have a similar structure to Merck's vaccine.Trial participants now must be warned about the potential riskshighlighted in the Merck trail if they participate in experiments thatuse a cold-virus carrier similar to Merck's product, Anthony Fauci,director of the National Institute of Allergy and Infectious Disease, said.

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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 vaccineuses three shots of DNA followed by a cold-virus booster shot, whichhas different components than the Merck vaccine. Nabel said he plans tomodify the study by testing the vaccine only on people with limitedexposure to colds and by increasing monitoring of patients.

Hildegund Ertl -- an immunologist at the Wistar Institutewho is preparing to test an experimental HIV vaccine that uses achimpanzee cold virus -- said the Merck trial also likely will affecther 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 notcause 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 Investigationreported that experimental HIV vaccines that typically use harmlessviruses called adeno-associated viruses might damage the immune systemby exhausting important cells, Reuters reports.

Accordingto the group, AAV vaccines when tested in mice directly interfered withimmune cells called CD8 T-cells, which are T-cells that a vaccine issupposed to stimulate to fight HIV. "The immune cells becomeexhausted," Ertl said, adding, "It is simply a defense mechanism ofT-cells -- if there is too much antigen for too long a time they simplyturn themselves off." The researchers said AAV vaccines should not betested on people until more studies are conducted. Ertl said it isunclear whether her findings contributed to the developments in Merck'strial, which used an adenovirus.

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

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

Reprinted with permission from kaisernetwork.org. You can view theentire Kaiser DailyHIV/AIDS Report, search the archives, and sign up for email delivery at kaisernetwork.org/email . The Kaiser Daily HIV/AIDS Report ispublished for kaisernetwork.org, a free service of The Henry J. Kaiser FamilyFoundation.

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