During childhood, most people become infected with a virus called cytomegalovirus, or CMV. Because this virus persists in its human hosts for life, usually without ever causing harm, scientists at Oregon Health & Science University theorized it might serve as an ideal vehicle for vaccinating people against HIV, the virus that causes AIDS.

The basic idea is straightforward: engineer the mild-mannered virus to carry a few genes from the deadly one to prime immune defenses to squelch infections. The harmless CMV virus's ability to persist indefinitely means that as a vaccine carrier, it could potentially produce lifelong immunity.

"It keeps large numbers of immune system soldiers out at the frontlines all the time, basically for life, waiting for that pathogen invasion, and it catches HIV early when it's still weak," says Louis Picker, a scientist at OHSU's Vaccine and Gene Therapy Institute and Oregon National Primate Research Center in Hillsboro.

To test the idea, Picker and colleagues used a strain of CMV that infects rhesus monkeys. They vaccinated 24 monkeys with the modified CMV and exposed them to a particularly nasty strain of SIV, the monkey equivalent of the AIDS virus. In 13 of the monkeys, the vaccine quickly stamped out infections, and protection lasted for at least a year in 12 of them, the researchers

in the journal Nature. Levels of SIV dropped to undetectable levels in most of the protected animals.

"It is so good at controlling the virus, it may be able to keep the virus permanently suppressed. If replicated in humans, that would be truly remarkable," says Dr. Jerome Kim, deputy director for science for the U.S. Military HIV Research Program, who was not involved in the OHSU work.

Despite decades of work, several big hurdles still stand in the way of an effective AIDS vaccine. Misleading animal studies set the stage for a disastrous clinical trial with a vaccine candidate made by Merck. The drug company halted the trial in 2007 when it became clear the vacine wasn't protecting volunteers – and may have made them more vulnerable.

In the biggest success so far, two vaccines used together appeared to lower the risk of infection by about 30 percent compared with placebo injections in a 2009 study involving more than 16,000 volunteers in Thailand. But the two-vaccine combination probably isn't effective enough for wider use.

Scientists haven't figured out a reliable way to make vaccines work against a virus that swiftly mutates into immensely variable forms. An immune attack mounted against one form can leave many others unscathed.

Conventional vaccines prime the immune system to act too slowly. They instill a memory for the invader, but the immune system needs many hours to generate a force of attack cells – too long to overcome HIV's rapid onslaught, in which one or two viral invaders can multiply into unstoppable billions.

Using CMV as a vehicle may

. In the study, vaccinated monkeys kept a protective force of killer T-cells in circulation. "Because CMV persists and constantly stimulates the immune system, it maintains combat readiness," Picker says.

A rapid response by the immune system could minimize the problem of variable mutants. The first invading HIV viruses haven't yet acquired all the mutations that allow them to evade the immune defenses of a new human host.

"It's a vulnerable period," Picker says.

How well it works against HIV in people remains to be seen. The OHSU researchers are studying why the CMV vaccine failed to protect half of the monkeys, and they're trying to figure out ways to make it work better. They also need to make sure that purposely infecting healthy people with an active virus won't cause more harm than good.

Ordinary CMV can unleash damaging attacks when it infects a developing fetus with minimal immune defenses, or an adult with a severely depleted immune system caused by drugs or an illness such as AIDS. CMV causes brain damage in about 8,000 newborns each year in the U.S. when women are first infected during pregnancy.

"The big question for self-replicating viruses is going to be safety," says Kim.

Picker is confident that his team can ensure safety. The researchers are considering ways to alter the virus to limit its ability to replicate in people. Picker figures it will take at least three years of work to make a vaccine candidate ready for human clinical trials.

--

; follow him on