AIDSWEEKLY Plus; September 16, 2002
Staff Medical Writers

The candidate vaccine - still early in developmental stages at the Institute of Human Virology (IHV) - is described in a report in the Proceedings of the National Academy of Sciences USA.¹ It is authored by Drs. Timothy Fouts, Anthony Devico, and colleagues at the IHV, a center of the University of Maryland Biotechnology Institute and affiliated with the University of Maryland Medical Center, and Dr. Ranajit Pal and colleagues at Advanced BioScience Laboratories, Inc., (ABL) in Kensington, Maryland.

One of the major challenges in developing an effective AIDS vaccine has long been the fact that the virus that causes AIDS, much like the influenza virus, exists as multiple strains that present many different faces to the immune system, said the authors. The surface of the AIDS virus, HIV, is coated with a protein called gp120 that has chemical features that vary from strain to strain. It has been difficult for researchers to find a single vaccine component that is able to generate antibodies that recognize the many forms of gp120 that exist in nature.

The IHV/ABL research team approached the problem by recognizing that all gp120 molecules have a shared characteristic that allows all HIV strains to bind a molecule on human target cells called CD4. Importantly, once gp120 forms a complex with CD4, it undergoes structural and chemical changes that reveal features shared by all HIV strains.

Taking advantage of this knowledge, the team produced artificial gp120-CD4 complexes that were chemically treated in order to glue or "crosslink" them together. The complexes were then used to generate antibodies in small animals and monkeys.

"The gp120-CD4 complex has shown a consistent ability to generate antibodies that neutralize a wide range of HIV-1 isolates," said Devico, assistant professor, IHV. "The preliminary findings indicate the gp120-CD4 complex might serve as a useful model for HIV vaccine development," he added.

Long the hope of AIDS researchers, it now appears that developing a single HIV vaccine for multiple viruses is indeed an increasingly realistic endeavor, according to IHV Director Dr. Robert C. Gallo.

"This is one of the more exciting findings that I have witnessed in HIV/AIDS research since the early days when it seemed scientific advances were announced regularly," said Gallo, who is also codiscoverer of the AIDS virus.

"From the beginning of the field of HIV/AIDS research, the most important goal was to develop a vaccine that prevents virus infection," said Gallo. "The difficulties have been many, spanning close to two decades. But this has the potential to bring us a major step forward in that ultimate quest. At the Institute of Human Virology, we will make this our prime effort."

The timing couldn't be more critical, he said.

"HIV/AIDS has overcome the 1918 influenza pandemic and bubonic plague of the 14th century to become the worst epidemic and deadliest disease in medical history," commented Dr. George Lewis, director of the IHV's division of vaccine development. "Twenty-five million persons have died worldwide, another 40 million are infected and the numbers are rapidly escalating second to second, he explained.

"While advances in therapeutics are helping many with the disease live longer and healthier lives," Lewis added, "most of the world lacks theses resources and our best bet to stop the AIDS epidemic is a vaccine. We hope this will become an effective tool toward that global goal."

Though designed as a preventative vaccine, the complex might also be useful as a therapeutic vaccine, said the authors. The gp120-CD4 complex will continue to be evaluated with regard to safety and immunogenicity within the next 2 years and should procede into Phase I clinical trials, according to Gallo.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

1. Fouts T, Godfrey K, Bobb K, et al. "Crosslinked HIV-1 envelope-CD4 receptor complexes elicit broadly cross-reactive neutralizing antibodies in rhesus macaques," Proc Natl Acad Sci U S A 2002 Sep 3;99(18):11842-7

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