On World AIDS Day, the Internet site WebMD trumpeted news so sensational it seemed destined for every front page: “It worked in mice. It worked in monkeys. And now in humans, a therapeutic vaccine has stopped HIV in its tracks.”
The treatment was startling not only for what it achieved, but how. Unlike conventional, preventive vaccines, a therapeutic vax can’t block infection. But it can help an HIVer’s damaged immune system contain the virus. Moreover, vaccine therapies act only on the immune system, not inside the cells that process HIV meds, so they avoid HAART’s daily dosing and side effects.
U.S. media, viewing preventive vaccines as the only vax headliners, largely ignored the story. But the study—and other recent therapeutic vax advances—is important to med-weary HIVers, and the results can’t be dismissed.
WebMD’s “HIV-stopping” therapy was the work of a team led by Jean-Marie Andrieu, MD, of Paris’ Institute of Research for Vaccines and Immunotherapies for Cancer and AIDS. While other vaccines have delayed HIV rebound during temporary HAART breaks for HIVers with undetectable viral loads, this one went further: It targeted mostly never-been-treated HIVers with viral loads from 13,000 to 300,000. After one series of shots, about half the participants saw impressive CD4 rises and viral-load drops lasting more than 12 months—some viral loads plummeted from hundreds of thousands to less than 1,000.
Andrieu’s team had injected 18 HIVers with a designer mix of their own HIV grown in their own dendritic cells (DCs). DCs are key players in the immune system, greeting foreign invaders such as HIV and escorting them to lymph nodes, where other immune cells should whack the intruders. But HIV normally subverts this process, allowing immune damage to progress. Andrieu programmed his subjects’ DCs to perform better, awakening killer cells to attack HIV successfully. (For a peek inside the lab, see “Seven Days to Vax,” right.)
In nearly half the participants, HIV levels fell more than 90 percent and stayed there for a med-free year. The only side effect, Andrieu says, was a painless swelling of the lymph nodes—indicating that the vaccine was turbocharging the immune system.
Not surprisingly, the vaccine didn’t work in everyone—those with higher initial CD4 counts responded best. And follow-up lasted only a year, so there’s no guarantee the numbers will hold without additional booster shots. What’s more, the study lacked a comparison group getting dummy immunizations. “The only thing Andrieu’s results prove is the need for a properly designed study,” quips Jon Cohen, who wrote the HIV-vax chronicle Shots in the Dark.
Vax experts like Julianna Lisziewicz, PhD, of the Research Institute for Genetic and Human Therapy, are more optimistic. “Andrieu’s results,” she says, “encourage us to continue human testing of this dendritic-cell approach in humans.” And Harvard’s Bruce Walker, MD, says the study “provides the first suggestion that therapeutic immunization alone—in the absence of HAART—may be effective.”
After a slew of failed attempts at creating a therapeutic HIV vax (remember Vaxsyn?), Andrieu’s results may signal a second coming for this treatment hope. Indeed, in the past year, two other vax giants (Walker and Brigitte Autran, MD, of Paris’ Hospital Pitié-Salpêtrière) have also accomplished what they call “proof of principle” with therapeutic vaccines: the first evidence that vaccines can augment the immune response to HIV in humans. At press time, other therapeutic vaccine trials were flourishing.
Like most researchers, Lisziewicz thinks therapeutic vaccines will merely supplement HIV meds, slowing resistance, minimizing viral blips, perhaps reducing drug doses. But Andrieu says he won’t be limited to a pill helper—he’s working to make his vax easier to prepare and test in larger groups. “This was the first Sputnik,” he says. “We don’t know how long it will take to get to the moon.” We’ve been promised the moon before—here’s to an actual landing.
Seven Days to Vax
Meet your immune system’s first line of defense: dendritic cells (DCs), star-shaped white blood cells that finger foreign agents like HIV. But HIV outsmarts the DCs, eliminating the eliminators. Andrieu’s vaccine offers your DCs the upper hand, letting your own immune system overpower HIV—without pills. The weeklong process begins and ends with you.
DAY ONE: You spend three hours hooked to a blood filter, which collects about 10 billion immature white blood cells (monocytes). Those are stirred into a soup with genetically engineered versions of your body’s chemical messengers (cytokines), allowing the monocytes to grow into dendritic cells (DCs).
DAY FIVE: For two hours, 100 million DCs are exposed to a billion HIV particles that have been isolated from your blood and chemically rendered noninfectious. The DCs memorize the virus, ingesting it, smashing it to pieces (peptides) and
displaying the viral peptides on their surfaces like wanted posters. Then the DCs mature and strengthen for two more days.
DAY SEVEN: You get four shots of these custom-made DCs, with their “I know HIV when I see it” expertise, suspended in a sterile saline solution—one in each arm and hip. Booster shots follow two and four weeks later. The specially trained DCs rush to your lymph nodes, where they teach CD4s to recognize HIV and killer CD8s to dispatch infected cells.
Off and Running
Unleash your inner guinea pig in one of these therapeutic vaccine clinical trials, now enrolling U.S. HIVers
|NAME/PHASE|| IT TWEAKS YOUR IMMUNE SYSTEM BY… ||WHERE/WHOM TO CONTACT|
| ACTG A5197, |
|Using three HIV genes inserted into a cold virus (“adenovirus-5”).||Tons of sites: go to clinicaltrials.gov for more information.|
| AI51181-01A1, |
| Using several HIV genes (plus IL-2) inserted into a canarypox virus (“ALVAC vCP1452”).||New York City: Aquanette Sass, 212.746.4361; firstname.lastname@example.org.|
| ACTG A5130, |
|Using ALVAC vCP1452 (see above) loaded into your DCs.||New York: Ann Marshak, 212.420.4519; email@example.com. Boston: Teri Flynn, 617.726.3819; firstname.lastname@example.org.|
| AI44628, |
|Using HIV peptides (small proteins) loaded into your DCs.||Boston: Kathy Habeeb, 617.726.3819; email@example.com and Rajesh Gandhi, 617.724.9690; firstname.lastname@example.org.|