Kenyan HIV variant provides clues for vaccine design

Strain of AIDS virus carries traits that make it vulnerable to human antibodies

Jan. 7, 2008

While studying a group of women at risk of HIV in Mombasa, Kenya, Dr. Julie Overbaugh and colleagues found a potential vulnerability in the AIDS virus that could lead to clues for designing an effective vaccine.

Photo by Susie Fitzhugh

Two simple changes in its outer envelope protein could render the AIDS virus vulnerable to attack by the immune system, according to research from the Human Biology Division’s Drs. Julie Overbaugh and Catherine Blish and undergraduate student Minh-An Nguyen.

The results, published Jan. 3 in PLoS Medicine, could provide important clues for designing an effective AIDS vaccine, desperately needed to decrease the number of new HIV infections, now estimated at about 2.5 million per year worldwide.

Although most people infected with HIV produce antibodies against the virus within several weeks following infection, these antibodies rarely prevent the infection from progressing to full-blown AIDS. This occurs partly because the virus rapidly mutates and escapes recognition by these antibodies. Thus, an important goal of HIV vaccine design is to find ways to expose conserved regions of the virus to antibodies.

While studying a group of women at risk of HIV in Mombasa, Kenya, senior author Overbaugh and colleagues noticed that one woman carried an AIDS virus that was easily inactivated by antibodies. Antibodies bind to an invader and neutralize it. They initially described this virus in 2002 and presented evidence in 2007 in the journal AIDS that the virus was unusual in its immunological properties.

Analyzing this woman’s virus for their current study, the researchers found that it contained mutations in four amino acids in the envelope protein, two of which, when introduced into unrelated strains of HIV in the laboratory, rendered each virus sensitive to a number of antibodies produced in people infected with HIV, including those directed to more conserved regions.

The researchers propose that these mutations cause a change in the overall structure of the envelope protein that results in exposure to the immune system of regions that are normally hidden.

“If further research confirms this idea, vaccines containing envelope proteins that include these mutations might better stimulate antibody responses to HIV,” said Blish, a postdoctoral fellow in Overbaugh’s lab. “We are currently exploring how these mutations alter the structure of envelope protein and whether these changes will improve vaccines.”