How HIV Neutralizing Antibody Works

A new avenue for the possible development of a vaccine against the virus that causes AIDS has been opened by a group of scientists that includes two Florida State University researchers.

The team reports in Friday's edition of the journal "Science" about their discovery that a human antibody known as 2G12 has a unique way of attaching to tiny proteins on the exterior of the human immunodeficiency virus (HIV) and neutralizing it.

Most antibodies bind to proteins and, as a defense, the HIV virus coats its surface proteins with a thick layer of carbohydrates. This process essentially tricks the immune system because it identifies the carbohydrates as being part of a healthy human cell. But the 2G12 antibody's unique structure and expanded binding surface allow it to bind strongly to the virus' carbohydrate coating.

"It'll neutralize the virus even as the virus tries to mutate its proteins to avoid detection," said FSU biology Professor Kenneth Roux, who has studied HIV for more than six years. "This suggests that maybe vaccines could be engineered to specifically target the carbohydrates for attack."

Such a vaccine might include something that would stimulate the human immune system to make 2G12-like antibodies when the HIV virus is present.

"If we could develop a vaccine that would induce this kind of antibody, it would be quite significant," Roux said.

Many existing vaccines work by stimulating antibody production, such as those for measles, polio, hepatitis B and hepatitis A.

Roux and FSU research associate Ping Zhu are among the 16 scientists who authored the paper. Daniel Calarese of The Scripps Research Institute in La Jolla, Calif., is the paper's primary author. In addition to FSU and TSRI, scientists from the University of Oxford, United Kingdom, and the University of Agriculture, Vienna, Austria, co-authored the research paper.

Roux said many months ago he saw with the help of an electron microscope that the 2G12 antibody could attach to the surface molecules on HIV, but the shape of the antibody was so unusual that he decided it needed further study. When he attended an AIDS vaccine conference in California last March, Roux compared notes with scientists from TSRI who, using different techniques, had seen the antibody's binding powers, too, and were similarly amazed at its structure. At that point, Roux said, "we knew we were on to something."

HIV causes AIDS by binding to and ultimately killing T helper cells, which are immune cells that are necessary to fight off infections by common bacteria and other pathogens. As HIV depletes the body of T helper cells, otherwise harmless microorganisms can produce lethal infections.

The World Health Organization estimates that around 40 million people are living with HIV worldwide. During 2001 alone, more than four million men, women and children succumbed to the disease, and by the end of that year, the disease had made orphans of 14 million children. In the United States, 40,000 people are infected with HIV each year.