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  • Jon is a contributing correspondent for Science.
 

Unusual AIDS Vaccine Shows Promising Results in Monkeys

11 May 2011 1:01 pm
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SIV surrenders. A monkey test of a new AIDS vaccine defeated a powerful strain of the simian version of HIV.

A new study gives a much-needed booster shot to the beleaguered AIDS vaccine field. The experiment, led by immunologist and pathologist Louis Picker of the Oregon Health & Science University in Beaverton, showed that an unusual approach to vaccinating against SIV (a simian cousin of HIV) protected 12 of 24 monkeys from a “challenge” with a particularly virulent strain of that virus. Specifically, all monkeys became infected, but in half of the animals, their immune systems drove the virus down to undetectable levels for more than a year.

“It’s the best result I’ve seen against the worst SIV known,” says the University of Wisconsin’s David Watkins, an immunologist who tests AIDS vaccines in monkeys and was not involved with the work. “I’m very excited by this approach.”

The vaccine contains SIV genes stitched into cytomegalovirus (CMV), a herpesvirus that harmlessly infects many humans and serves as the delivery vehicle, or vector, for the AIDS virus proteins. Typically, AIDS vaccines use vectors that quickly die, but CMV stays alive indefinitely and constantly confronts the immune system with the mock version of the enemy. As a result, Picker contends, the immune system stays on high alert and can respond to an attack by SIV much more quickly. “The whole game changes when you talk about early interception of the virus,” he says.

AIDS researchers have long debated which specific immune responses correlate with protection, and this study—published online today in Nature—is reigniting that discussion. Picker contends that a novel type of T cell response plays a critical role in why the vaccine works, but others find the evidence for that less than compelling. “I’m not sure what the protective mechanism is in these experiments,” Watkins says.

Most vector-based AIDS vaccines train what are known as central memory T cells to recognize the virus. Upon a real infection, these cells expand and mount an attack. But, Picker says, “it’s too late and too little to handle [AIDS] viruses.” With the CMV vector, monkeys developed high levels of so-called effector memory T cells, which do not go through an expansion phase and remain ready to do battle at all times. Other experiments suggested that these cells were key and that only CMV rouses them. Picker’s team vaccinated monkeys with a variety of vectors bearing SIV genes, but none of them triggered effector memory cells. Monkeys receiving these other vaccines and challenged with the same highly pathogenic SIV (known as mac239) handled the virus little better than control animals that did not receive any vaccine. “Our vaccine is completely different than all the other vaccines and works completely differently,” Picker says.

Picker suspects that the monkeys that received CMV vaccines but failed to control the challenge virus did not generate high enough levels of effector memory cells in their tissues. He’s looking for ways to augment the effector memory response and would like to combine the CMV vaccine with one that elicits antibodies against SIV and, ultimately, HIV.

Currently, Picker’s team has no plans to move the vaccine into human studies because of safety concerns about CMV. The virus causes no harm in healthy people and is widespread, infecting nearly half of the U.S. population and more than 90% of people in sub-Saharan African and India. Still, it can hurt fetuses, leading to vision and hearing loss as well as mental retardation, and, in an ironic twist, can cause blindness in immune-deficient children and adults who have diseases like HIV infection. Picker’s group is now trying to make a weakened CMV that cannot cause disease under any circumstance. “We’re fairly far along on it,” he says. “But we’re going to have to prove that it’s safe and still protective.”

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