Ten years after the then US President set a target of ten years for developing an AIDS vaccine, it still remains a distant dream .

"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).

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.

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 cellsa 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.

Currently 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. In this week's New England Journal of Medicine Anthony Fauci, director of
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