A glimmer of a path to an AIDS vaccine

By Michael Gerson -

In the 3-D model on the computer screen, the AIDS virus resembles a deformed head of broccoli, its clustered surface constantly shifting. Researchers at the National Institutes of Health’s Vaccine Research Center attribute moral characteristics to their enemy; it is “deceptive” and “diabolical.” The virus is covered in a cloak of sugars that mimic natural proteins, making it invisible to the immune system. Its true nature is only revealed to the body when the virus needs to get into a cell — latching onto a protrusion and injecting its genetic poison with a spring-loaded harpoon. It protects itself by constantly changing its genetic sequence. A person infected by one version of the virus, in a matter of weeks, can carry a million small mutations.

During its 30-year march, the virus has infected 65 million human bodies. Thirty million men, women and children have died. There is not a single example of an infected person whose immune system cleared the virus from his or her body.

This is the largest challenge for the vaccine researcher. The immune system has effective responses to diseases such as polio, measles or smallpox. Many people recover and gain immunity. The body itself proves that a vaccine is possible. But there is no naturally protective response to the AIDS virus. Medical researchers have to do better than nature.

During the decade following the creation of the Vaccine Research Center by President Bill Clinton, scientists gained a better understanding of the virus. But their main discovery was how difficult it would be to defeat. There was not even a scientific route to a solution. “It was like the ancient Greeks looking for a path to the moon,” recalls structural biologist Peter Kwong.

An audit of the center in 2008 would have found billions of dollars spent on few answers. But scientific progress often comes fitfully. “You do the groundwork,” says Gary Nabel, director of the center, “and then it pops.” In 2009, there were two unrelated breakthroughs. A Thai vaccine trialmanaged to produce a small protective effect, though researchers did not know why. At about the same time, improved diagnostics found that 10 to 25 percent of people with HIV produce antibodies that neutralize the virus — though the response is too weak and too late to make a difference.

The virus, it turns out, is vulnerable in one place. There is a portion of its cloak that can’t shift and camouflage itself — the small area where the virus latches on to the target cell. An antibody with the same footprint as the cell can block the attachment.

Scientists at NIH have now cloned that antibody. Produced in large enough quantities, it can be injected. Testing is scheduled to start next year. But even if this approach works, injecting manufactured antibodies won’t be an immediately practical solution. A gram of the antibody, Nabel estimates, might cost $100 to produce. Perhaps 100 million people would need to be injected once a month. This approach would be prohibitively expensive until costs are dramatically reduced.

The greater hope is a vaccine that could be injected once or a few times, producing an immune response that gives sustained protection. “We want the body to be the manufacturing plant for the antibodies,” explains Nabel. Unlike the precedent of other vaccines, it isn’t possible to use a dead version of the virus to produce immunity. It may be necessary to break off just the vulnerable bit of the virus, then introduce it into the body to provoke the production of antibodies. “It is not a fictional idea,” Nabel assures me. But it hasn’t been done before.

In the short and medium terms, neither injected antibodies nor a vaccine will be a substitute for other forms of AIDS prevention. Large reductions in infection rates can be achieved through consistent condom use, behavior change and circumcision. The treatment of HIV-infected pregnant women with AIDS drugs can prevent transmission to their children.Microbicide gels are promising.

But researchers at NIH know that an effective vaccine would be a decisive defeat for their wily enemy. “Every day there are 7,000 new infections,” reflects Nabel. “If we do our work a day sooner, it would make a difference.”

The day that work is finished remains distant. But now, at least, there is a path to the moon.