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 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.
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 the National Institute of Allergy and Infectious Diseases, discusses prospects for an AIDS vaccine. He says while the ultimate goal is prevention, much like that for polio, smallpox and measles, combating the AIDS virus requires a non-traditional strategy in which a vaccine may not totally block infection, but could lower the level of virus and slow down transmission.
Fauci says these interim vaccines would work in tandem with the two-dozen or so antiviral therapies currently available.
The hope is that an effective human T-cell vaccine could substantially improve the quality of life for people who contract the virus after immunisation by postponing the day when they develop HIV and Aids and have to begin treatment with a daily cocktail of drugs.
Anthony Fauci says the success of the disease-modifying vaccines could be a major advance in the development of an AIDS vaccine. About 40 million people are HIV-positive and another 11 000 people contract the virus every day, most of them in the world's poorest nations.
The ability of HIV to mutate rapidly remains one of the biggest obstacles to a successful vaccine. The DNA 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.
Various attempts are made, like the current trials, but each with its own problems. Experts concede that a fully effective AIDS vaccine is a long way off. "There are people who will tell you we will never have a vaccine—I can't say those people are wrong," says infectious disease specialist Scott Hammer of Columbia University.
But "you shouldn't be in this business if you don't have some degree of optimism based on the science. The world needs an AIDS vaccine. To give up now is selling the science short."