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The search for an effective AIDS vaccine suddenly looks more promising

Since the AIDS epidemic burst upon us in 1981, scientists have feverishly sought a vaccine to protect people from this deadly and incurable disease. But the path to a vaccine has not been easy. Twenty years and 600,000 American AIDS cases later, an effective AIDS vaccine still eludes the best efforts of researchers.

One problems has thwarted all efforts: The HIV virus that causes AIDS has an unusually mistake-prone DNA copying enzyme. Making mistakes here and there as it produces offspring virus particles, HIV generates mutations at a prodigious rate. That is why few of those infected with HIV have exactly the same virus.

Why is this a problem to vaccine researchers? To understand, you need to look for a moment at the way the antibody proteins induced by a vaccine defend you from virus infection. Antibodys don’t attack viruses, but rather the cells infected by viruses. Each antibody trys to fit itself onto one of the virus proteins that almost always adhere to the surface of infected cells. Like matching two fingerprints, the match must be precise. When there is a perfect match, the antibody sounds a molecular alarm and the immune system kills the infected cell.
A vaccine works by exposing you to a protein of the disease-causing virus. Researchers use genetic engineering to insert an HIV gene into the DNA of an otherwise harmless virus. The engineered virus exposes you to that one HIV protein only -- the claw of a lion, not the whole dangerous HIV package -- so the immunization doesn’t make you sick.

Your immune system responds to this call-to-arms by recruiting to your body’s defense antibody-making cells, each able to make the antibody that recognized the HIV protein. Soon there are millions of these cells, each industriously churning out the virus-recognizing antibody.

Now you should be protected. If HIV infects you in the future, your blood is awash with antibody proteins waiting to pounce on any HIV-infected cells and stop the AIDS infection before it gets started.

Only it doesn’t.

Why not? The genes of HIV mutate so frequently that no two strains of HIV are alike. A vaccine targeted against one version is ineffective against others. Like a thief of many disguises, HIV is able to dodge any antibody a vaccine throws against it.

For 17 years this problem has seemed insurmountable, but last week researchers at Emory University led by Harriet Robinson reported a solution. They seized on a property of mutation so obvious it had been largely overlooked -- mutations are accidents. A strain of HIV may produce numerous mutations as it proliferates, but each of these mutations occurs as a random mistake in a different virus particle. No two particles produce the same mutation.

The key to an effective vaccine, then, is to use more than one HIV protein. Robinson used three. Any one virus might have mutated to be different from one of the three proteins, but the probability of all three proteins being mutated in the same virus particle is about the same as lightening striking the same person three times -- very, very small.

Not contented with this innovation, the Emory team set out to boost the power of the immune defenses. The human body has another line of immune defense called the cell-mediated response. Why not bring this to bear as well?

In a double-barreled attack on HIV, the researchers first infected 24 monkeys with a circular piece of DNA containing three HIV genes. Such naked DNA readily infects human cells. Once inside, it directs the production of the three HIV proteins. Passing to the cell surface, these proteins create a mock-HIV infection that kicks cell-mediated immunity into action. To the immune system, the cells look HIV-infected. Rushing to the body’s defense, the immune system produces killer cells that wait in ambush to attack and destroy any body cells displaying one of the three proteins.

A few weeks later, the researchers administer the same three HIV genes to the monkeys, but this time the HIV genes are stitched into a harmless virus. Introduced this way, they activate a monkey’s antibody defenses instead of its cell-mediated immunity. Within a few days, a burst of antibodies is produced directed against the three HIV proteins.

Seven months later, the 24 vaccinated animals were “challenged” by inoculating them with a laboratory version of HIV. Called SHIV, it is a genetically engineered version that is part HIV (to make it lethal) and part simian AIDS virus (to make it infect monkeys).

The vaccine worked! Even 20 weeks after the SHIV challenge, 23 of the infected monkeys continued to control the infection, and still had healthy immune systems. Four unvaccinated control animals, by contrast, all developed full-blown AIDS and died.

It is difficult to avoid hope at this exciting development. However, keep in mind that this is an SHIV vaccine, developed for monkeys. There is no guarantee that it will work with humans. Many exciting discoveries fail to clear this last critical hurdle. But in 20 years, no candidate AIDS vaccine has looked so promising. An HIV version of the vaccine is slated to begin human trials by early next year.

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