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Envelope vaccines have been shown in other laboratories to protect safely primates challenged with an immunodeficiency virus sharing the same HIV envelope, as illustrated in August by research reported in the Proceedings of the National Academy of Sciences by scientists at Harvard Medical School. The St. Jude multi-envelope AIDS vaccine strategy is unique in combining 23 different envelopes that represent many different isolates of HIV.

"Our ultimate aim is to discover the number and mix of HIV proteins, gathered from HIV isolates found throughout the world, which will be effective in preventing infection regardless of the isolate to which people are exposed," says Julia Hurwitz, Ph.D., a co-developer of the St. Jude multi- envelope AIDS vaccine with Karen Slobod, M.D., respectively of the Departments of Immunology and Infectious Diseases at St. Jude Childrens Research Hospital.

The Phase I safety trial approved in September by the FDA will get underway immediately, beginning with the recruitment and evaluation of 9-18 eligible, healthy human volunteers, and is expected to last one to two years.

"At St. Jude Hospital we are very proud of the progress Drs. Slobod, Hurwitz and their colleagues have made in bringing the St. Jude multi-envelope AIDS vaccine to its first trial and they have our strongest possible support as they and their colleagues continue to pursue an AIDS vaccine," said Arthur W. Nienhuis, M.D., Director of St. Jude Childrens Research Hospital.

Although every viral envelope consists of proteins called gp120 and gp41, each envelope looks different to the immune system because the proteins vary, much like human faces differ from each other. These differences have been an obstacle to vaccine development.

Scientists at St. Jude Childrens Research Hospital have built upon the knowledge obtained by other vaccine research groups to select the building blocks -- or backbones -- for their HIV vaccine. One backbone is the smallpox vaccine that globally eradicated smallpox in humans by the late 1970s. St. Jude Childrens Research Hospital is using 23 different HIV envelopes each contained in a smallpox vaccine backbone to constitute the first component of the St. Jude multi-envelope AIDS vaccine.

The St. Jude research team is also developing vaccine boosters as part of the vaccine program. Boosters include a DNA vaccine in which injected DNA prompts the production by the body's cells of envelope proteins that then stimulate the immune system. The DNA vaccine strategy was co-developed by Robert Webster, Ph.D., chair of the Department of Virology and Molecular Biology at St. Jude Childrens Research Hospital. Drs. Slobod and Hurwitz may also deliver a booster of purified envelope proteins.

The incorporation of many envelopes in the St. Jude multi-envelope AIDS vaccine strategy is aimed at representing a cross section of virus envelopes that have emerged in developing and developed regions of the world during the 15-year global epidemic. Collecting the HIV envelopes, isolating the envelope sequences and other related research efforts were initiated at St. Jude Childrens Research Hospital four years ago.

"Although complete implementation of this vaccine strategy will take years, we are moving as quickly as possible without sacrificing attention to safety, quality and the St. Jude commitment to excellence," says Dr. Slobod.

While testing the safety of the St. Jude multi-envelope AIDS vaccine during the upcoming Phase I trial, the St. Jude research team will also measure volunteers' immune system response to the vaccine by evaluating their B cell (antibody) and T cell (cellular) immune responses. These data may be a preliminary indication of volunteers' expected immune response to the vaccine during later trials. The St. Jude team constructed the vaccine in a manner that will permit determination of whether immune system responses are the result of vaccination or actual HIV infection unrelated to the vaccination.

Since the late 1980s, St. Jude Childrens Research Hospital has also been active in developing treatments for children with AIDS. It is part of the AIDS Clinical Trial Group, a national cooperative research network which allows pediatric AIDS researchers across the country to share resources and information.

St. Jude Childrens Research Hospital, in Memphis, Tenn., was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is primarily supported through funds raised by the American Lebanese Syrian Associated Charities (ALSAC). All St. Jude patients are treated regardless of their ability to pay. ALSAC covers all costs of treatment beyond those reimbursed by third party insurers, and total costs for families who have no insurance.

SOURCE St. Jude Childrens Research Hospital

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