Ten years ago President Bill Clinton set a national goal to develop an AIDS vaccine within a decade. At that time, the human immunodeficiency virus (HIV) that causes AIDS had infected some 25 million people worldwide. Clinton established a research center at the National Institutes of Health and pledged to enlist other nations in the effort.
“There are no guarantees,” he said in a speech delivered at Morgan State University announcing the initiative. “It will take energy and focus and demand great effort from our greatest minds. But with the strides of recent years, it is no longer a question of whether we can develop an AIDS vaccine, it is simply a question of when.”
Infectious disease experts cautioned that the goal was overly optimistic. They were right. Today there is still no vaccine, despite an increasingly organized global effort and the quadrupling of funds committed to it. “We have learned in that period of time how formidable an adversary HIV is,” says Wayne Koff, senior vice president for research and development at the International AIDS Vaccine Initiative (IAVI).
The vaccine search suffered its latest disappointment in September, when investigators called an early stop to a clinical trial of a much anticipated new type of HIV vaccine. Like many other candidates now in testing, it was designed to coax the immune system's disease-killing T cells into attacking the virus more aggressively. Experts say that such a vaccine is unlikely to prevent HIV infection. But they hope at least one candidate will weaken the virus enough to delay the complications of AIDS and to reduce the need for expensive antiretroviral drugs.
Increased funding and more sophisticated organization have played a key role in getting the project this far. “By the early to mid-1990s the AIDS vaccine effort was relatively moribund,” says IAVI president Seth Berkley, who founded the group in 1996. “It's 100 percent a scientific problem; however, without an enabling environment, you can’t solve the science.”
Global spending for HIV vaccine research increased from $186 million in 1997 to $759 million in 2005, according to the Joint United Nations Program on HIV/AIDS. The IAVI helped to move the field forward by establishing research consortia so that investigators could more easily coordinate and exchange information. The group partnered with governments and vaccine makers to conduct trials outside the U.S., which account for nearly half of the 30-plus trials currently in progress. The NIH formed its own HIV vaccine trial network in 2000 to oversee clinical research sites in the U.S., Africa, Asia, the Caribbean and South America.
The scale of the effort reflects the scientific challenges. In the early 1980s, after identifying the HIV virus as the cause of AIDS, researchers were at first confident that they could come up with a vaccine against it within a few years, Koff says. Vaccines work by exposing the body to a disease-causing agent or a fragment of it. That exposure primes the immune system to produce a flood of antibodies that stick to the infecting organism and block it from entering cells. Researchers identified a protein on the surface of HIV, dubbed gp120, that enables the virus to infect and then slowly destroy so-called helper T cells, which regulate immune responses. The gp120 protein seemed like a good candidate for an HIV vaccine.
And early tests of a gp120 vaccine looked promising. But optimism faded by the early 1990s as researchers learned the vaccine worked only against strains of HIV that had adapted to conditions in the laboratory. In 2003 results finally came in from a phase III clinical effectiveness trial of a gp120 vaccine manufactured by VaxGen: it failed to prevent infections or reduce the number of virus particles circulating in the blood. (A related vaccine, VaxSyn, based on the gp160 protein [see illustration at left], never progressed to late-stage clinical testing.)