STILL SEARCHING: Ten years after President Bill Clinton announced a national goal of creating an AIDS vaccine within the decade, researchers may be on the threshold of a partially effective vaccine, but complete prevention is still a distant goal. Image: © ISTOCKPHOTO/LISE GAGNE
Ten years ago today, President Bill Clinton announced a national goal to develop an AIDS vaccine within a decade. At that time, the Human Immunodeficiency Virus (HIV) virus that causes AIDS had infected some 25 million people worldwide. Clinton established a research center at the National Institutes of Health (NIH) and pledged to enlist other nations in the effort.
"There are no guarantees," he said in a speech delivered at Morgan State University in Baltimore 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. A decade later, 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 immunologist Wayne Koff, senior vice president for research and development at the International AIDS Vaccine Initiative (IAVI).
The next two years will reveal whether researchers are on the right track for at least a partially effective vaccine. Three clinical trials are underway to test the effectiveness of coaxing the immune system's disease-killing T cells into attacking the virus more aggressively. Experts say that such a vaccine is unlikely to prevent the HIV infection. But they hope it will weaken the virus enough to delay the complications of AIDS and reduce the need for expensive antiretroviral drugs.
Increased funding and more sophisticated organization have played a key role in getting 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 move the field forward by establishing research consortia so investigators can more easily coordinate and exchange information. The group partnered with governments and vaccine makers to conduct trials outside of the U.S., which now account for nearly half of the 30-plus trials currently underway. 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 confident they could come up with a vaccine against it within a few years, says Koff. Vaccines work by exposing the body to the disease-causing agent or a fragment of it, which primes the immune system to produce a flood of antibodies that stick to the infecting organism and block it from entering cells.
HIV infects so-called helper T cells, which regulate the immune response, and slowly destroys them. Researchers rapidly identified the molecule that grants HIV entry into those cells—a surface protein called gp120, which inserts itself into CD4 receptor molecules on the helper cells.
Early tests of a gp120 vaccine looked promising, but optimism faded by the early 1990s as researchers learned the vaccine only worked against strains of HIV that had adapted to conditions in the laboratory. In 2003 results finally came in from a phase III clinical trial of a gp120 vaccine manufactured by VaxGen: It failed to prevent infections or reduce the number of virus particles circulating in the blood.
By then, HIV researchers had turned to the idea of energizing killer T cells by injecting DNA-encoding genes from circulating strains of the virus. This approach entails using a partially disabled, non-HIV virus to infect and deliver the HIV DNA to the cells that the delivery virus would normally infect. This stimulates the cells to produce the corresponding HIV proteins and display them on their surfaces to attract helper and killer T cells.