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Immune boost

A potent "vaccine-plus" prevents AIDS in monkeys

A new AIDS vaccine has prevented monkeys injected with a highly virulent strain of the AIDS virus developing the disease.

Although the vaccine didn鈥檛 stop infection, levels of the virus in the inoculated monkeys were almost undetectable after 140 days.

The potent 鈥渧accine-plus鈥 contains not only DNA from the HIV virus but also immune system proteins. The proteins are very effective at boosting levels of killer T cells, says Norman Letvin of the Beth Israel Deaconess Medical Center in Boston.

鈥淲e haven鈥檛 yet made a vaccine that will prevent AIDS virus infection in humans,鈥 he stresses. 鈥淏ut our findings suggest that our potential vaccine might also slow disease progression after an infection has occurred and decrease the likelihood of an infected individual transmitting the virus.鈥

鈥淭his could have important ramifications for the AIDS epidemic, and it could potentially improve the quality of life and lifespan of infected individuals,鈥 he says.

Human trials of HIV vaccines have not been very successful, says Sarah Rowland-Jones, who has been working on a vaccine at the University of Oxford. 鈥淪o far, no one has got very excited by any of the human trials. If the team has managed to get a good immune response that鈥檚 very important.鈥

Twin track

The new vaccine consists of HIV DNA plus interleukin-2 and a portion of the protein, immunoglobulin G. Interleukin-2 stimulates T cell activity, and immunoglobulin G helps prolong IL-2鈥檚 life in the bloodstream.

The team gave eight rhesus monkeys the DNA vaccine alone, eight the vaccine-plus, and eight a placebo. They then injected the monkeys with a powerful hybrid of HIV-1 and SIV, the monkey version of the virus.

After 140 days, the eight monkeys inoculated with the vaccine-plus showed no signs of the disease and had higher than normal levels of both killer T cells and helper T cells. Half of the monkeys that had received the placebo had died and two of the monkeys that had received only the DNA vaccine developed the disease.

鈥淥bviously it is very important to see whether the effects of the vaccine persist in the long term,鈥 says Letvin. 鈥淲e will be monitoring all the monkeys very closely.鈥

Enhanced killing

There is evidence that boosting levels of HIV antibodies may in fact help the virus be carried through the bloodstream. So vaccine researchers are working on alternative approaches including ways of enhancing killer T cell activity, says Rowland-Jones.

To date, the best way of boosting human killer T cell levels has been to use a vaccine made from HIV鈥檚 DNA and followed that with a live replicating vector. This vector is usually a relatively harmless virus engineered to produce HIV proteins, and so boost the immune system response.

Human trials of this approach are currently taking place in France and the US, for example. But Rowland-Jones says those vaccines are not very potent. 鈥淎dding interleukin-2 could easily make a big difference,鈥 she says.

More at: Science (vol 290, p 486)

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