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medpundit |
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Tuesday, February 25, 2003The trial took place at 59 sites, mostly in the continental United States, with some in Canada, Puerto Rico and the Netherlands. It involved 5,400 volunteers, mostly men, none of whom were infected with H.I.V. at the start of the trial. About 5,100 of the participants were gay men who said they had had sex with many other men. The other 300 were women who were considered at high risk of infection through sexual contact. Two-thirds of the participants were given a series of seven shots over three years, while the other third were given the same number of placebo injections. The goal was to see if the people who received the vaccine would have a lower rate of infection. In the overall population of participants, 5.8 percent of those who received the placebo became infected, compared with 5.7 percent of those who received the vaccine. The difference was not statistically significant. But among black, Asian and other minorities the rate of infection was only 3.7 percent in the vaccinated group, compared with 9.9 percent in the placebo group. That meant, after statistical adjustments, that the vaccine reduced the infection rate in that group by 66.8 percent. The numbers were small, about 500 patients, but statistically significant. There was a less than 1 percent chance that the findings were the result of chance. Why the difference among minorities isn’t yet clear. But here’s how the vaccine works: The vaccine, known as Aidsvax, is made from a protein called gp120, the same protein that protrudes from the surface of H.I.V. and helps the virus dock with cells of the body's immune system. The protein in the vaccine is made in genetically engineered hamster ovary cells. Since the vaccine consists of only one protein and not the whole virus, it cannot give someone AIDS. But it is designed to provoke the immune system into making antibodies that will latch on to the gp120 protein in the real virus and the virus from infecting immune cells. Last week’s New England Journal had an article (Sorry. Requires subscription.) that explains why this approach isn’t such a good one. It turns out that the protein, gp120, is extremely flexible and difficult for antibodies to latch on to: The initial event in HIV-1 infection is the stable tethering of HIV-1 to a host cell. This interaction is mediated by a binding event between the glycoprotein (gp) 120 molecule that protrudes from the virus and a CD4 molecule on the host cell. (An accessory host-cell molecule, CCR5, is also involved in the binding event.) Stable binding leads to infection. The binding reaction can be blocked by neutralizing antibodies, but only two antibodies are known to bind glycoprotein 120 stably. The majority of antibodies fail to bind glycoprotein 120 and therefore do not neutralize infection. A recent study shows that glycoprotein 120 is refractory to the binding of these "impotent antibodies" because the molecule is unusually flexible, and the binding regions of the antibodies are specific to a particularly flexible part of it. (Emphasis mine.) Just a speculation, but it could be that minorities produce better binding antibodies. Anyway, the article predicted the failure of VaxGen’s vaccine. In an aside the author’s mentioned that the company might want to reconsider their approach. Turns out they were right. But give the company credit, they presented their findings honestly and didn’t try to use statistics to exaggerate them. posted by Sydney on 2/25/2003 06:06:00 AM 0 comments 0 Comments: |
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