WASHINGTON, D.C--Unsuccessful attempts to unravel how a vaccine against the monkey version of the AIDS virus actually works have led to renewed calls for testing a similar--but potentially risky--vaccine in humans. The findings were reported here at the 4th Conference on Retroviruses and Opportunistic Infections.
About 5 years ago, primate researcher Ronald Desrosiers of Harvard's New England Regional Primate Research Center reported that he and his co-workers had developed a vaccine made from weakened SIV, the simian cousin of HIV. This "attenuated" virus did not itself cause disease in monkeys, and it protected the animals from whopping doses of virulent strains of SIV.
To tease out how the vaccine worked, Desrosiers's team bled monkeys immunized with the attenuated SIV vaccine and purified the antibodies that were found in their blood. They injected the antibodies into two monkeys that had not received the vaccine. As a control, two monkeys received a generic preparation of antibodies and two others received antibodies that in test tube studies can prevent infection with a virulent SIV strain. Three hours after infusing the six animals with these various preparations, the researchers injected the monkeys with a virulent SIV. Within a few weeks, all six became infected.
Desrosiers concluded that the vaccine does not operate by the most obvious mechanism: stimulating the immune system to make antibodies that can then block the virus before it infects cells. "Antibodies do not seem sufficient to confer the protections accorded by the [attenuated vaccine]," Desrosiers said. So what could be protecting the monkeys? AIDS researchers speculate that the vaccine may trigger immune killer cells to destroy HIV-infected cells or stimulate production of immune-system messengers called chemokines that can block a receptor used by SIV to enter cells and establish an infection.
Because of the difficulty of determining why this vaccine works, Desrosiers and several researchers argue that an attenuated version should simply be tested in people. They point out that most vaccines against other pathogens moved into clinical trials before researchers figured out how they worked. But others argue that weakened HIV, once injected into a person, could mutate into a virulent form and cause AIDS. The fact that HIV integrates into the host cell's DNA also poses the risk of triggering cancer. "The scientific leadership has really been against the idea of moving forward with this vaccine," said pediatrician John Sullivan of the University of Massachusetts, Worcester, in a presentation yesterday morning. However, he argued, "it's important for the scientific community to begin to lobby for this."
Sullivan noted that one of his patients and seven other transfusion recipients infected by the same bad lot of blood in Australia are infected with attenuated HIV strains that look similar to Desrosiers's engineered vaccine. These people, Sullivan said, have never shown AIDS symptoms. He suggested that 10 or so patients with a terminal illness who have less than a year to live could be asked to volunteer to receive an attenuated HIV vaccine.
At least one prominent group is hoping to move the attenuated strategy closer to human trials. The International AIDS Vaccine Initiative, sponsored by the Rockefeller Foundation, recently announced that it's interested in funding further work on the approach to evaluate its potential risks and benefits.