Novel HIV vaccine set for clinical development

Sep 3 2007

A promising new HIV vaccine created at The Wistar Institute has received funding for clinical development aimed at moving the vaccine into human clinical trials as soon as possible.

With $13.3 million in funding over five years, the planned trials will be conducted under the auspices of the Integrated Preclinical/Clinical AIDS Vaccine Development Program of the National Institute of Allergy and Infectious Diseases. The Wistar Institute scientists will collaborate with researchers at Emory University, the University of Pennsylvania, Harvard School of Public Health, MRC/UVRI Uganda Research Unit, and the National Institute for Communicable Diseases in South Africa. The start date for the project is September 1.

“We believe our vaccine, which is built on a novel chimpanzee virus backbone, has unique immunological advantages over other HIV vaccines currently in testing,” says Hildegund C.J. Ertl, M.D., professor and Immunology Program leader at The Wistar Institute. Ertl, principal investigator for the newly funded project, is also director of the Wistar Institute Vaccine Center. “In preclinical studies, the vaccine induced a vigorous immune response in monkeys, and we are hopeful it will do the same in humans.”

Many vaccines currently in development are based on modified human adenoviruses, known as vectors, that incorporate genetic elements from target pathogens to stimulate a protective immune response to those pathogens. These vaccines can work well, but there is an unaddressed problem with this approach, which is that many people receiving the vaccines will have pre-existing immunity to the human viruses upon which they are based, largely negating their effectiveness. About 45 percent of adults in the United States, for example, have pre-existing immunity to a strain of human adenovirus being used as an HIV vaccine vector in current clinical trials.

To circumvent this potential difficulty, the Wistar-led team has developed a series of vaccine vectors based on chimpanzee adenovirus strains, which possess the immunological strengths of human adenoviruses without their drawbacks. The Wistar vaccine will undergo early stage clinical testing for safety and then for its ability to induce an immune response. In the latter trial, the vaccine will be given as a four-part series of inoculations.

Another important aspect of the new HIV vaccine is that it seeks to stimulate a cellular immune response to HIV rather than an antibody response. The cellular immune response corresponds to the T-cell arm of the immune system, while the antibody response corresponds with the B-cell arm of the immune system.

“Based what we know about HIV and the immune system's response to the virus, it may not be possible to create a vaccine that generates antibodies able to neutralize HIV,” says Ertl. “For this reason, we and others are now focusing our attention on developing a vaccine that stimulates the production of anti-HIV CD8+ T cells, which have been shown to reduce viral load, although they do not prevent infection. Our vaccine has induced unprecedented levels of activated CD8+ T cells in experimental animals, and we are eager to see if it can perform as well in humans.”