Important note: Information in this article was accurate in 2009. The state of the art may have changed since the publication date.
Los Angeles Times - November 18, 2009
Thomas H. Maugh II
The adenovirus is what is known as a vector. It is used to carry genes from, in this case, the AIDS virus into cells in the body, where they can produce proteins that stimulate immunity to HIV. Merck used a vector called adenovirus serotype 5 (Ad5), from which they removed genes that could cause disease. Ad5 is very similar to adenoviruses that cause colds, and there's the rub, according to Dr. Steven Patterson of Imperial College London, who led the new study, appearing this week in the Proceedings of the National Academy of Sciences. Many of the patients in the study had previously been exposed to closely related adenoviruses and had built up immunity to the virus.
But that immunity did not simply destroy the vaccine vector. In addition, it attracted T cells that were meant to kill the virus to the mucosal membranes in the nose, mouth and genital areas. Those cells are the primary targets for HIV. "Our research suggests that the adenovirus-based HIV vaccine effectively instructs the cells that HIV infects to gather round exactly where HIV is likely to be introduced," Patterson said. "This is clearly worrisome for this kind of vaccine. Scientists are currently developing adenovirus-based vaccines to protect people from TB and malaria as well as HIV, but they may have to rethink those vaccines if the effect we describe in our new paper is a problem for all of them."
Patterson and his colleagues studied the phenomenon in laboratory dishes using samples obtained and frozen during the initial trials of the vaccine. Two other recent studies in humans concluded that the adenovirus was not the problem. But such negative results, Patterson said, can be difficult to interpret. In particular, those earlier studies looked for the T cells in the blood, and Patterson believes the simplest explanation is that the cells migrated out of the blood into mucosal tissues.
Merck responded that the researchers may be jumping to unwarranted conclusions. "It would be premature to suggest that this provides an explanation for the STEP results, and the implications for other vaccines or gene therapy are unclear," Dr. Michael Robertson, director of vaccines clinical research for the company, said in a statement.
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