For decades, the human immunodeficiency virus (HIV) has confounded researchers trying to eradicate it. It has a maddening ability to mutate. But researchers at The University of Texas Medical School at Houston, reporting at the XVII International AIDS Conference in Mexico City, August 3–8, 2008, discovered that some patients with HIV produce powerful antibodies that prevent it from attaching to cells.
The researchers were led by Sudhir Paul, PhD, professor and director of the chemical immunology research center at the Houston medical school. They found that the adept antibodies produced by certain patients with lupus and by long-term nonprogressors (LTNPs), patients infected with HIV for many years without progressing to full-blown AIDS, acted against gp120. gp120, a glycoprotein on the surface of the HIV envelope, helps the virus adhere to the host’s lymphocytes, white blood cells that are part of the immune system. The antibodies in the lupus and LTNP patients not only block the site where the virus normally attaches to the lymphocyte, but also remain intact, repeating their performance.
Immunologists have studied gp120 for more than 10 years. While all people exposed to HIV produce catalytic antibodies against gp120, some do not produce enough to prevent it from slowing or stopping infection. Efforts to pinpoint the location of gp120 were stymied by the protein’s ability to hide from the host’s immune system. HIV needs one region on its envelope that remains constant, otherwise it cannot attach and infect cells. Other portions of the protein hide the gp120, preventing the host’s immune system from identifying it as foreign. The host’s body makes antibodies against the changed regions of HIV, but not the region where it attaches.
Paul and colleagues identified the 13-unit strand of amino acids on gp120 where the virus attaches itself to the lymphocytes. Stephanie Planque, a graduate student in Paul’s lab and a member of the team, screened antibodies from lupus patients, searching for those that had catalytic activity against the select strand. She performed the same screen with long-term nonprogressor patients with hemophilia. Antibodies purified from three people with hemophilia—each of whom had HIV for more than 17 years—killed HIV samples from five families of the virus.
Paul’s lab then created engineered abzymes, antibodies with enzymatic activity, from the patients. “The abzymes recognize essentially all of the diverse HIV forms found across the world,” says Paul. “This solves the problem of HIV changeability.” Typical antibodies can’t keep up with the ever-changing virus; they inactivate one virus particle at a time. In contrast, one abzyme molecule can permanently degrade thousands of virus particles.
Researchers, although years away from the development of an HIV vaccine, are heartened by the breakthrough. “HIV is an international priority because we have no defense against it. Left unchecked, it will likely evolve into even more virulent forms,” Paul says. “We have learned a lot from this research about how to induce the production of the protective abzymes on demand.”