Vaccines are supposed to stop you getting sick. But in one of the biggest HIV vaccine trials yet, not only did the vaccine not work, it may have made people more susceptible to infection. It may not even be the only HIV vaccine to backfire in this way.
The STEP trial was one of only two so far aimed at preventing HIV infection. Since 2004, 2675 people at high risk of contracting HIV have received either a vaccine made by US drugs giant Merck, or a placebo, at 19 sites in North and South America and Australia. They also got condoms and counselling on how to avoid HIV, and were tested for it each month.
The trial stopped in September when it emerged that as many people had been infected with HIV after the vaccine as on the placebo. A similar trial in South Africa was stopped for the same reason. Then in October participants were warned that those who鈥檇 received the vaccine might be at greater risk of HIV.
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鈥淚n October participants were warned that those who鈥檇 received the vaccine might be at greater risk of HIV鈥�
The results 鈥� described as 鈥渄isappointing and puzzling鈥� by Anthony Fauci, head of the US National Institute of Allergy and Infectious Diseases which helped fund the trial 鈥� were revealed at a meeting in Seattle, Washington, last week. Merck鈥檚 vaccine is a live, weakened adenovirus carrying three genes for HIV proteins.
Of 1836 men in the trial, 49 got HIV after the vaccine, and 33 after the placebo. This was enough to show that the vaccine didn鈥檛 protect them, although not quite proof that it made infection more likely. However, closer analysis of the data suggests that men who already have some immunity to adenoviruses 鈥� a common cause of colds 鈥� were more likely to be infected with HIV if they were given the vaccine.
They might have been at higher risk of HIV for other reasons 鈥� for example, more of the men with high immunity to adenoviruse were uncircumcised. However, Hildegund Ertl of the Wistar Institute in Philadelphia adds that people with more antibodies to adenoviruses might, through several mechanisms, have produced more activated CD4 cells in response to the vaccine. These are precisely the white blood cells HIV invades. In people with frequent exposure to HIV, even a temporary increase in CD4 cells means a greater risk of infection. Trial participants are now being studied to find out exactly what happened.
Several other HIV vaccines in clinical trials are also made from weakened live viruses, and work from Ertl鈥檚 lab to appear this week in the () suggests that the completely different adeno-associated virus might also reduce resistance to HIV, though by a different mechanism. AAV-based vaccines were being tested in two small safety trials in Africa, but the trials are ending early because the vaccines prompted little immunity.
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