A team of researchers says that the reason why the STEP trial of an experimental vaccine against AIDS failed could be partially because it made some people's immune cells more vulnerable to HIV infection.
Lead researcher Eric Kremer, of the University of Montpellier in France, said that the research group examined why people participating in the STEP vaccine trial who had previously been exposed to a cold virus, adenovirus 5, seemed more likely to become infected with HIV-1 than those who hadn't been exposed to the virus.
Some researchers had speculated that since the STEP vaccine's backbone was made from a modified version of adenovirus 5, it might be recognized by pre-existing antibodies in people who had previously been infected with this virus and eliminated from the body before an immune response to HIV-1 could develop.
However, Kremer's team discovered that when antibodies to adenovirus 5 were combined with the vaccine backbone in a culture dish, they triggered a pathway that causes the activation of certain immune cells called T cells, which are targeted by HIV in their active state.
The researchers revealed that in cell culture, T cells succumbed to HIV-1 infection three times more quickly than did those in a mixture that lacked adenovirus 5 antibodies.
According to them, their findings show how injecting an adenovirus-5-based vaccine into people with adenovirus 5 antibodies could have created a "chronic permissive environment for HIV-1 infection"1.
Warner Greene, the director of the Gladstone Institute of Virology and Immunology in San Francisco, who was not involved in the work, said that the study's results indicated that HIV-1 "encounters a singularly target-rich environment favouring successful HIV transmission" in people who had previous exposure to adenovirus 5.
However, there are many researchers who are not convinced that the new findings explain what went wrong in the original trial.
The experiments conducted by the research group were done in culture dishes, and did not use cells or antibodies taken from individuals who were actually involved in the STEP trial.
"I think that it outlines a very interesting hypothesis that might explain some of the STEP data," Nature magazine quoted Larry Corey, leader of the HIV Vaccine Trials Network, which conducted the STEP trial, as saying.
But he cautions: "One should recognize that the data presented are still largely in vitro and that further experiments to define whether this occurred among vaccinees in STEP need to be done."
Jonathan Yewdell of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, says that he is "dubious that this mechanism plays an important role in the HIV trial findings," because the events that it suggests make cells more vulnerable to HIV are probably "too transient to account for infections occurring weeks after vaccination."
"They're building on a series of reasonable hypotheses, but there are lots of alternative ways this could be happening," says Jeffrey Ravetch of the Rockefeller University in New York.
He, however, still hailed the attempt to find out why the STEP trial failed.
"It's a very important exercise. You have to try to understand what went wrong so you can design the next (vaccine) with that information in mind," he said.