The Best Defense? A Monkey's Death Complicates Effort to Find HIV Vaccine

Starting in 1999, Dr. Dan Barouch and his mentor, veteran HIV scientist Norman Letvin, both at Harvard, immunized eight monkeys with an experimental vaccine and then tested it by injecting a lethal AIDS virus into the animals. The vaccinated monkeys got infected, but they didn't get sick -- until the early summer of 2000, when blood tests indicated changes in the way the immune system of monkey 798 was responding to the AIDS virus. At first, Barouch didn't know what was happening, but over the next few months, an astonishing account -- published in today's issue of the journal Nature -- emerged of how the AIDS virus evaded the vaccine-boosted immune system, causing the monkey to sicken and die.

"It is sobering to find that a single point mutation within the virus can initiate a cascade of events resulting in clinical vaccine failure and death," the researchers wrote. Barouch insists that the study "is not the death knell for these kinds of vaccines." Indeed, seven of the eight vaccinated monkeys remain perfectly healthy. "The cup is 7/8ths full, not 1/8th empty," Letvin said.

The fate of monkey 798 highlights the scientific gamble that some of the world's foremost research institutions and pharmaceutical companies are taking on the AIDS crisis. As the epidemic sweeps through the poorest regions of the world, infecting more than a fifth of adults in some sub-Saharan African countries, many researchers are betting on the development of a "partial protection" vaccine that would allow the virus to secure a toehold in the body rather than repel it completely. If partial-protection vaccines prevent AIDS or delay it for a long time, they would give HIV-infected individuals a longer life. And because they suppress the amount of virus in the body, they could also reduce transmission of the disease. But if they postpone the onset of disease for only a short time, as in monkey 798, they might actually worsen the epidemic.

Scientists have been forced to settle for partial-protection vaccines because the classical approach to immunization -- introducing the production of antibodies that block the virus from infiltrating cells -- has proved devilishly difficult for HIV. So researchers are trying to stimulate a different arm of the immune system: killer T-cells. Squadrons of these cells can prevent or delay the onset of symptoms, but not, apparently, bar the virus from infecting the body.

Despite this news, much of the field remains optimistic about a vaccine. Letvin and Barouch tried several vaccines on their animals, and monkey 798 got the second-best one. Vaccines that induce a stronger immune response would almost certainly work better, and Letvin has said that the best Merck vaccine looks more potent than any he has used.

Back to other CDC news for January 17, 2002

Previous Updates