WASHINGTON -- In 1987, two young medical researchers, Anthony Fauci and Cliff Lane, conducted the first clinical trial of an AIDS vaccine. They took the envelope that surrounds the virus and simply injected it into study participants, hoping to get an immune response -- an approach that had worked on Hepatitis B. It failed on AIDS.
Thus began one of history's most consequential scientific detective stories.
AIDS, it turns out, is very different from its viral relatives. Polio, for example, infects quickly, then clears the body. AIDS survives and replicates for years. To exist, it has evolved unprecedented mechanisms to escape the immune system. It is cloaked in sugar molecules, which the body doesn't recognize as a threat. And its viral shell is constantly mutating to avoid the attachment of antibodies.
"Evolution is a smart foe," Fauci told me in a recent interview. In virology, smart means deadly. When exposed to polio or measles, more than 90 percent of people get better -- their immune system works. For the vast majority infected with AIDS, there is no protective immune response.
But herein lies the hope: In a minority of cases -- about 20 percent across the world -- the immune system does respond, adapting to the constant adaptations of the AIDS virus. But instead of coming in one or two weeks, the needed antibodies are produced in one or two years. By then it is too late.
Too late for the patient to be protected from infection, but useful for the researchers studying their immune response. At the Vaccine Research Center at the National Institutes of Health, researchers have developed high-resolution images of the AIDS virus at the atomic level. They have now identified four sites -- called epitopes -- where antibodies can bind to the surface of the virus and physically prevent duplication. (Antibodies are clunky things, about a third the size of the virus, that latch on by fitting the contours of the epitope.) These areas are conserved -- meaning that the functioning of the virus requires their shape not to mutate too much. Scientists, in short, have identified a few vulnerable parts of the shield.
Targeting each of these four epitopes has pros and cons. Some are essential to the process of the virus entering the cell but harder for antibodies to access. Others are more exposed. An effective approach will go after more than one.