United Press International - Thursday, January 14, 1999
Lori Valigra

The work is still in a very early stage, with experiments having been done only on mice. But the approach opens up new ways for researchers to develop an effective vaccine that could be used worldwide to prevent the spread of HIV and AIDS, said Jack Nunberg, lead author of the study and director of University of Montana's biotechnology center. The research was reported today in Friday's issue of the journal Science.

Several HIV vaccine candidates have been tested in small groups of humans, but to date only one has U.S. Food and Drug Administration approval to be tested widely in a Phase III clinical trial in the United States. The vaccine, made by VaxGen Inc. of South San Francisco, Calif., is made from genetically engineered forms of two subtypes of HIV. Tests of the vaccine began last year, and results are not expected for several years.

These earlier vaccine efforts focused on creating an immune response, or antibodies, to a protein known as gp120 that forms part of the coat of the HIV virus. Vaccines are made from weakened strains of a virus or parts of a virus that provoke the body to produce antibodies to neutralize a virus infection. But the gp120 protein-based vaccines did not create the hoped-for immune response.

Nunberg and his colleagues suspected another part of the HIV virus coat known as the gp41 protein might also be needed to awaken antibodies.

For the HIV virus to infect a human cell, the HIV coat must bind to a human cell receptor known as CD4, and then fuse with the cell and inject the virus contents into it. The virus creates a sort of tunnel through which to do this.

David Montefiori, associate professor at Duke University Medical Center in Durham, N.C. and an AIDS vaccine researcher, likened the complex fusion process to a flower in which the gp120 is the flower petals and the gp41 is the stamen. When the gp120 "petals" come into contact with a human cell, they open up, and the gp41 "stamen" fuses the contact points and opens the tunnel so the virus can enter and infect the cell.

The opening of the petals lasts only a few seconds, which is why it has been hard to devise a vaccine that can act against the HIV virus.

Nunberg and his colleagues figured out a way to freeze open the "petals" and provoke antibodies to neutralize the HIV virus. The new concept is called a "fusion-competent" vaccine.

"I think a lot of people will be rethinking how to develop vaccines now," Nunberg said. "We've discovered a new way of thinking about developing an HIV vaccine that takes into account the underlying functioning of the coat protein."

Montefiori said: "I was very excited when I first heard about it. This is the first time anyone has ever been able to generate these kinds of antibodies."

"But it's still in an early stage of development, and there's a lot more to do" he added. Montefiori reviewed the study in a separate article in Science.

Nunberg added that more basic research needs to be done to understand how a vaccine might work. He also said the new vaccine concept will soon be tested in Rhesus monkeys, which are more similar to humans than mice.

More than 40 million people worldwide are expected to be infected with HIV by 2000, according to the U.N. AIDS Report.

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