Why Don't We Have an HIV Vaccine?
The Virus that Causes AIDS is Breaking All the Rules
Human immunodeficiency virus (HIV) is proving to be a tough customer. In 1984, Robert Gallo discovered that acquired immune deficiency syndrome (AIDS) is caused by HIV. Shortly thereafter, he declared that a vaccine to deal with the virus—and thus prevent AIDS—would be forthcoming within two years.
Seven years later, President Clinton stated, “…an HIV vaccine will be developed in a decade’s time.” As the HIV epidemic in Africa and the Caribbean raged into 2003, President Bush asked Congress to appropriate $15 billion to address this scourge. For people already infected, antiviral medications remained the backbone of therapy, but the prospect for an effective vaccine remained elusive.
Ongoing Frustration with HIV Vaccine Trials
In late 2007, trials for the latest in a long string of vaccine possibilities were curtailed, as some of the study subjects were actually shown to have a higher likelihood of HIV infection following a dose of the test vaccine.
"There is something very, very peculiar" going on in the vaccine trials, said Anthony S. Fauci, head of the National Institute of Allergy and Infectious Diseases.
In that brief declaration, Dr. Fauci summarized two decades of painstaking research—and bitter disappointment—that has surrounded HIV and its treatment: HIV is a peculiar bug, and more than 20 years following its identification, we still have no vaccine for it.
HIV Foils Classic Vaccine Theory
By their nature, vaccines must activate some part of our immune system in order to do their job. Usually, this is achieved by introducing a weakened or killed form of an infectious agent—or, perhaps, a “deactivated” piece of that agent—into the bloodstream, whereupon the immune system recognizes the agent as a foreign invader and mounts a vigorous response to eliminate it. The immune system then “remembers” the invader so it won’t be a problem in the future.
Unfortunately, either by evolutionary design or pure misfortune, HIV has developed ways to get around our usual immune defenses and thwart vaccine development. First, the virus infects a population of T lymphocytes called CD4 cells—the very cells that are responsible for telling the rest of the immune system that a virus has invaded the body. Once inside a CD4 cell (and it can hide there for years) HIV splices into the cell’s DNA where it remains invisible to the remainder of the immune system.
When HIV finally reactivates and replicates within infected cells, it produces an assortment of copies with different coats. Eventually, when the CD4 cells die (effectively reducing the number of “messenger cells” that could spread the alarm), the hodgepodge of viruses released into the bloodstream confounds the immune system’s ability to react. The new HIV particles move on to the next CD4 cell and the cycle begins anew.
Unraveling the Mystery of HIV
We don’t have a vaccine for HIV because this virus doesn’t follow the usual rules. And, though our knowledge about this agent has grown exponentially since its discovery, we still know relatively little about its biology. For example, how do some people who are repeatedly exposed to HIV manage to avoid infection? Why does a specific genetic variation that protects some people from catching malaria perversely make them more likely to be infected by HIV? And why does a promising candidate for a vaccine paradoxically increase one’s risks for infection?
The answers to these questions—and to those yet to be posed—will lead us ever closer to an effective vaccine for this troublesome virus.
