The National Institute of Allergy and Infectious Diseases (NIAID) has begun the first human trials of an experimental vaccine containing several copies of a chemically synthesized protein fragment, or peptide, of HIV, the virus that causes AIDS.
The Phase I trial will examine the product's safety and immune-stimulating ability in 36 uninfected men and women at low risk of HIV infection. Volunteers between the ages of 18 and 60 are being recruited in St. Louis, Mo., and Rochester, N.Y., through NIAID's AIDS Vaccine Clinical Trials Network, says study coordinator Geoffrey Gorse, M.D., of the St. Louis University School of Medicine.
Peptide vaccines have two particular strengths: they are inexpensive and relatively easy to modify," comments Margaret I. Johnston, acting deputy director of NIAID's Division of AIDS (DAIDS), "to include new mixtures of peptides and those from different HIV strains." With such flexibility, Dr. Johnston says, peptide vaccines have the potential to stimulate a broad range of immune responses to accommodate significant changes in the virus as they occur.
Recent studies indicate that HIV strains now fall into at least five genetically distinguishable groups. Scientists have expressed concern that protection in one individual over time or of people in different countries may be difficult to achieve with a vaccine made from a single virus strain, says Patricia Fast, M.D., who heads the HIV vaccine clinical trials effort in DAIDS.
The prototype vaccine incorporates eight copies of one peptide from the MN strain, representative of a common U.S. strain. The vaccine manufacturer, United Biomedical, Inc. (UBI), of Hauppauge, N.Y., eventually wants to develop a multicomponent vaccine incorporating a mixture of peptides capable of providing protection against worldwide strains of HIV.
The peptide used in the vaccine lies on the surface of HIV in an area known as the V3 loop. Scientists have identified the V3 loop as a primary site that stimulates immune reactions to the virus. Almost all candidate vaccines in NIAID-sponsored trials so far have been subunit vaccines -- genetically engineered proteins of HIV such as gp120 or gp160 -- made from single HIV strains. UBI's vaccine is the eighth product and first peptide vaccine studied by NIAID's network, and one of several novel HIV vaccines expected to enter NIAID trials this year.
The NIAID trial will evaluate three doses of the vaccine. For each dose, 10 volunteers will be chosen at random to receive the vaccine containing alum adjuvant, a substance that boosts specific immune responses. Two volunteers will receive a placebo, alum alone. Neither the participants nor the health care workers will know who gets the vaccine. Each volunteer will receive a primary injection into the muscle and booster shots one and six months later. Dr. Gorse and his colleagues will immunize volunteers with the low-dose vaccine first and move to the next higher dose only after determining that the lower dose is safe.
For more information about the trial, call the AIDS Clinical Trials Information Service at 1-800-TRIALS-A, open weekdays 9:00 a.m. to 7:00 p.m. EST, or the individual units at the numbers listed below.
St. Louis University School of Medicine St. Louis, Missouri Geoffrey Gorse, M.D./Robert Belshe, M.D. Contact: Carol Berry (314) 577-8649
University of Rochester Medical Center Rochester, New York Michael Keefer, M.D./Raphael Dolin, M.D. contact: Shirley Erb (716) 275-5871
Geoffrey Gorse, M.D./Robert Belshe, M.D. Contact: Carol Berry (314) 577-8649
Rochester, New York Michael Keefer, M.D./Raphael Dolin, M.D. contact: Shirley Erb (716) 275-5871