Where is the AIDS Vaccine?

Science gets closer, but a fully effective vaccine against HIV remains elusive

By then, HIV researchers had turned to a different idea for a vaccine. They inserted segments of HIV genes into the DNA of partially disabled non-HIV viruses. The resulting viruses could deliver the HIV genes into cells without causing a lethal infection. Infected cells would produce and display HIV proteins, however—thereby energizing the immune system's T cells to attack those proteins wherever they might appear.

Merck, along with the federally funded HIV Vaccine Trials Network (HVTN), initiated a phase II clinical proof-of-concept trial in late 2004 to quickly study the effectiveness of its adenovirus-based vaccine containing three HIV genes. In September a peek at the data revealed that participants injected with the vaccine had contracted HIV no less often than had those receiving a sham. Investigators halted the study, which had enrolled 3,000 people in the Americas and Australia, as well as a second trial begun in 2006 in South Africa. In the coming months, researchers hope to figure out why the vaccine failed and how to improve the remaining crop.

Next up for rapid testing is a broader-spectrum vaccine developed by the NIH's Vaccine Research Center (VRC). Sanofi-Aventis is conducting a phase III clinical trial in Thailand of its product, which combines a canarypox virus vaccine with VaxGen's gp120 vaccine. Results are due as early as 2008.

“The immune response and the safety so far have put these out there further than the other candidates we have,” says disease specialist Scott Hammer of Columbia University, part of the team designing the VRC vaccine trial.

Studies in monkeys seem to support the concept, says immunologist David Watkins of the University of Wisconsin–Madison. Watkins and his colleagues reported in 2006 that rhesus monkeys injected with four genes from the simian immunodeficiency virus—which causes an AIDS-like disease in monkeys and apes—were no less susceptible to infection by the identical strain of the simian virus than were unvaccinated monkeys, but they did maintain lower levels of virus in their blood for up to a year after infection. Another group reported that vaccinated monkeys were more likely to survive three years after infection than unvaccinated animals were. “That was pretty encouraging,” Watkins says. But he cautions against putting too much weight on the early results.

The ability of HIV to mutate rapidly remains one of the biggest obstacles to a successful vaccine. Its genetic material is prone to errors during duplication and replicating HIV molecules frequently exchange pieces of genes. Because of this instability and the potentially rapid life cycle of the virus, the genetic sequences of HIV particles in a single person can be as diverse as those of all the influenza viruses in the world. A vaccine that produces an immune response against one HIV sequence may have no effect on other strains.

To address this problem, the VRC vaccine contains three variants of the HIV envelope gene—the gene that most readily mutates to resist treatment. The HVTN began a second trial of Merck's vaccine last February in South Africa, where the circulating virus differs from the one on which the vaccine is based.

T cell–stimulating vaccines may help destroy cells infected with HIV, preventing them from reproducing. But experts say they probably would not trigger the immune system to make antibodies and would therefore be only partially effective. “You’re trying to control replication, not prevent infection,” Watkins says. “Although, who knows? Maybe a T cell vaccine could do that.”

Merck and the HVTN called their test “STEP,” because a successful T cell vaccine would be only a step toward full protection—but it could be a highly significant one. The IAVI estimates that even a 30 percent effective vaccine given to just 20 percent of those at risk would avert 5.5 million infections worldwide between 2015 and 2030—or 11 percent of all estimated new infections for that period. A 70 percent effective vaccine administered to twice as many patients could avert 28 million infections.

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