AIDS Vaccine Tests Well in Monkeys

With the help of two proteins that enhance the immune system’s response to infection, an experimental AIDS vaccine has kept rhesus monkeys healthy for more than 4 months after they were exposed to a virus that causes acquired immune deficiency syndrome.

The monkeys still became infected with the virus, which in this case was a fusion of simian and human immunodeficiency viruses (SIV and HIV). But the animals’ bolstered immune system kept the infection from progressing to full-blown AIDS.

Unlike most vaccine strategies, this approach achieves only modest antibody production. Instead, it relies mainly on the formation of immune cells called killer T cells. These cells attack virus-infected cells, making it harder for the virus to spread and cause disease, at least for the short term, says study coauthor Norman L. Letvin, an immunologist at Harvard Medical School in Boston.

“If we could do this in humans, and if the effect was long-lasting, then it clearly would be a major advance,” says Robert Siliciano, an immunologist at Johns Hopkins Medical Institutions in Baltimore.

HIV overwhelms the body’s defenses by invading and destroying immune system sentinels called CD4 T cells. The virus mutates rapidly and hides in the body, making it hard for the immune system to eradicate.

Letvin and his colleagues used a DNA-based vaccine that encodes two proteins, one found on SIV and the other on HIV. Once produced in the monkey’s body, these proteins—while not infectious themselves—attract the attention of the immune system. While past studies have shown some success in spurring an immune response using DNA vaccines, “the general experience in this field is that it’s been hard to induce high levels of neutralizing antibodies to HIV,” Siliciano says.

Sidestepping antibodies and focusing on killer T cells seemed like a practical alternative, Letvin says.

To strengthen the vaccine, the researchers added either two naturally occurring mammalian proteins called interleukin-2 and immunoglobulin G or the DNA that encodes those proteins. Interleukin-2 revs up the manufacture of killer T cells, and immunoglobulin G extends the half-life of interleukin-2.

T cells become specific killers when presented with protein cues. Once programmed to seek a particular protein, these cells work like bloodhounds on a trail, sniffing out and latching onto anything displaying that molecule. Primed by the proteins encoded by the AIDS vaccine, killer T cells attacked virus-infected CD4 T cells.

Meanwhile, the interleukin-2 induced rapid proliferation of the killer T cells. In the monkeys that were given the new vaccine, a very high percentage—between 18 and 40 percent—of all circulating killer T cells were specifically programmed to lock onto the AIDS viral protein, Letvin says. This strongly suggests that killer T cells were responsible for suppressing AIDS in the monkeys, he says.

The researchers gave eight monkeys a series of injections of the new vaccine over 9 months. When exposed to the combination AIDS virus 6 weeks after the last dose, none became ill, nor did any develop the disease over the next 140 days. These monkeys also maintained their CD4 T cell counts, the scientists report in the Oct. 20 Science. The new vaccine worked well whether it contained interleukin-2 and immunoglobulin G proteins or the genes encoding these proteins.

Of four other monkeys, given the AIDS vaccine without the protein boosters, two became sick. Seven of eight monkeys that didn’t receive any vaccine but were exposed to the virus became very ill, and four died during the study.

Other research teams are also investigating how to use immune proteins to stimulate killer T cells against AIDS. Letvin suggests this could become a major strategy for developing a vaccine.

“Killer T cells elicited by vaccine cannot prevent infection but might change the clinical outcome of the infections,” he says.

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