San Francisco Chronicle - November 29, 2004
Sabin Russell at srussell@sfchronicle.com.

Although the technique is cumbersome and costly, the experiment published in an online version of the British journal Nature Medicine is being touted as "the first demonstration of an efficient therapeutic vaccine against AIDS."

The vaccine was tested in Brazil on 18 volunteers who were already infected with HIV, the virus that causes AIDS, but who were not yet taking any antiviral drugs. After four months, the level of HIV in their bloodstreams had been reduced an average of 80 percent.

By the end of one year, eight patients in the group had maintained a 90 percent reduction in virus particles in their bloodstream. Four of those patients had virus levels so low that they were comparable to so-called "long- term non-progressors," a rare cohort of people infected with HIV who never seem to get sick.

Unlike a conventional vaccine, this one cannot block infection from occurring. However, if the French technique could be perfected, it has the potential to keep some HIV-infected patients healthy without their having to take the three-drug "cocktails" of toxic antiviral drugs.

Instead, a series of injections, perhaps once a year, would keep their chronic infections in check.

The lead investigators in the French study are Drs. Jean-Marie Andrieu and Wei Lu of the Institute of Research for Vaccines and Immunotherapies for Cancer and AIDS, in Paris.

In an interview, Andrieu estimated that the cost of the annual therapy could be $4,000 to $8,000, less than a year's course of antiviral drugs. He said the only side effect of the therapy was a swelling of the lymph nodes, which caused no pain. The swelling was, in fact, an indicator that the vaccine was marshalling the body's immune system properly to ward off the AIDS virus.

No new patients have been enrolled in the experiment, but Andrieu said future research will attempt to understand "why it works in some people, and not in others.''

Although the experiment falls short of a breakthrough against AIDS, it represents a rare piece of good news in the field of vaccine research, which has been marked in recent years by a string of setbacks.

UCSF doctor sees cause for hope

"This is just a preliminary study, but it is encouraging,'' said virologist Dr. Jay Levy of the UCSF AIDS Research Institute. Levy did not participate in the research but is familiar with its findings.

Further studies are needed, Levy said, to learn exactly why the vaccine worked better than other, similar versions. A critically important step would be to determine whether the vaccine also reduced the amount of virus in sexual fluids. If it did so, a population of HIV infected individuals treated with the therapeutic vaccine would be less likely to transmit the virus to others. "The purpose of a real vaccine is to protect a population. This would have that advantage,'' Levy said.

At present, however, the vaccine is difficult to produce, and impractical to deliver to large numbers of people. This therapeutic vaccine is essentially custom-made for each patient who takes it.

To make a dose of vaccine, the French doctors extract from each HIV- infected patient a sample of dendritic cells -- starfish-shaped white blood cells that play a special role in the human immune system. They also take a sample of the virus from the infected blood of each patient.

In the laboratory, they separately grow uninfected dendritic cells and a batch of the virus itself. The virus is eventually killed and mixed in with the dendritic cells, whose special function then becomes vital.

The dendritic cells consume the virus, breaking it into pieces and displaying the parts on their surfaces like grisly trophies.

Doctors then inject the dendritic cells back into each patient.

Lymph nodes receive the message

Inside the body, the dendritic cells migrate to the lymph nodes, carrying their message of an invading microbe to resting banks of "killer" white blood cells. The broken bits of HIV on the dendritic cell's surface help to program these killer cells to recognize the virus -- like bloodhounds given a scent to chase. Once activated, they will seek out and destroy any cell in the human body that is infected by HIV.

It is a system of "cellular immunity" that the body routinely uses to protect itself. The AIDS virus, for reasons not fully understood, has managed to hijack the process. Dendritic cells are, in fact, one of the favored targets of living HIV, and once it ferries HIV to the lymph nodes, it then infects other white blood cells, making more copies of itself, and eventually depleting the cells.

The French laboratory intervention, by mixing dendritic cells outside the body with killed HIV, seems to restore their proper defensive role when they are returned to the body.

It is this focus on dendritic cells, and the use of a whole, killed virus, that distinguishes the French effort from other attempts to make a therapeutic vaccine.

Any optimism about the French experiment must be tempered with caution. The history of AIDS vaccine research is littered with failure. An attempt by British and Kenyan scientists to use this concept of cellular immunity to make a preventive vaccine was abandoned in August after a trial in Nairobi showed it did not stir up a strong enough response to protect against HIV.

Laboratory experiments with a similar vaccine that showed great promise in monkeys have slowed after further studies showed the virus was able to mutate into a vaccine-resistant strain.

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