Merck has announced that the Phase IIb efficacy trial of their HIV vaccine candidate will be doubled in size, recruiting 3,000 volunteers at high risk for HIV infection instead of the originally slated 1,500. A rather uninformative article appears in today's Wall Street Journal: http://www.aegis.com/news/wsj/2005/WJ050907.html Background about the trial can be found on the TAG website at: http://www.aidsinfonyc.org/tag/tagline/0407.html#2 and in TAG's recent pipeline report: http://www.aidsinfonyc.org/tag/tx/pipelineReportJuly05.pdf
The expansion of the trial is due to an alteration in the entry criteria. The Merck vaccine uses a virus called adenovirus serotype 5 (Ad5 for short) as a "vector" for carrying dummy HIV components into the body and thereby triggering immune responses against HIV. Unfortunately Ad5 is common in the environment (it causes severe colds) and many people have been exposed to it during their lives. As a result, many people have antibodies against Ad5, and high levels of anti-Ad5 antibodies have been shown to reduce the ability of Merck's vaccine to trigger HIV-specific immune responses. For the efficacy trial, Merck originally decided to include only individuals with very low levels of anti-Ad5 antibodies (a titer of less than 200). The company wanted to study their vaccine under ideal conditions to see if the type of immune responses it triggers (CD4 "helper" T cells and CD8 "killer" T cells) could offer any protection against HIV infection and/or disease progression.
According to the Wall Street Journal article, in a recent study it was found that "volunteers got a strong immune response even if they previously had developed antibodies to the adenovirus because of prior cold infections." Exactly what study is being talked about is unclear. But the upshot is that individuals with titers of anti-Ad5 antibodies higher than 200 are now being allowed to enroll in the phase IIb efficacy trial. TAG is querying Merck about the details and will post more information as we get it.
UPDATE 9/28: Janet Skidmore, Merck's vaccine PR person, tells us that the trial is now stratified: 1,500 enrollees will have anti-Ad5 antibody titers <200 while another 1,500 will be allowed to have a titer >200 with no upper ceiling. Apparently new studies using the latest "trivalent" version of the vaccine (that encodes the Gag, Pol and Nef proteins of HIV) found that the presence of anti-Ad5 antibodies affected the immunogenicity less than was seen in earlier studies which used a monovalent construct that encoded only the HIV Gag protein. We also have to digress and congratulate Janet on her recent marriage to Emilio Emini, former Director of Vaccine Research at Merck and one of the giants of the HIV research field.
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