BOSTON - Two Phase I clinical trials to test an investigational AIDS vaccine are currently underway at Beth Israel Deaconess Medical Center (BIDMC). The first of the two separate studies involves normal, healthy adult volunteers; the second involves HIV-infected patients.
BIDMC is the only site in Boston for the first trial, according to senior investigator Clyde Crumpacker, M.D., Infectious Disease Specialist in the Virology Research Clinic at BIDMC and Professor of Medicine at Harvard Medical School's Division of AIDS. The study, which will include a total of 160 participants at 10 sites throughout the U.S, will test a new "Ad5-HIV gag" recombinant vaccine being developed by Merck Research Laboratories. The study of HIV-infected patients will include 86 participants at 20 sites across the country, including BIDMC and Massachusetts General Hospital.
Both trials will test the safety of the investigational vaccine, as well as its capacity to create an immune response. Because the vaccines are produced through genetic engineering techniques, they do not contain live HIV virus and, therefore, cannot cause an infection.
"This new recombinant vaccine is composed of an adenovirus - a virus responsible for the common cold - to which a small portion of DNA from the HIV virus has been added," says Crumpacker, explaining that this combination works to stimulate the immune system's production of CD8 or "cytotoxic killer T cells." In individuals with the HIV virus, the CD8 cells then go on to target the HIV-infected cells for destruction.
Unlike a majority of vaccines - including, for example, the measles vaccine - which work by preventing the possibility of infection, the Ad5-HIV gag vaccine is designed to be both prophylactic and therapeutic.
"With antiretroviral treatment of HIV, we have learned that the immune system has a great capacity to restore itself," explains Crumpacker. "We're hoping that through the use of this new vaccine, HIV-infected patients can become 'long-term nonprogressors,' who lead healthy, functioning lives."
Phase I testing is conducted to determine how well the body tolerates the vaccine and whether and to what degree healthy individuals will develop protective immune cells to the HIV virus. Study participants at BIDMC are now receiving the first of three doses of the vaccine. The second and third doses will then be given at intervals of four weeks and 26 weeks after the first dose. Patients in the study will be followed for two years.
"AIDS is a daunting scientific challenge," says Crumpacker. "The main job of an HIV infection is to destroy an immune system that has evolved over millions of years to protect us from harm. Over the years, we've learned that viruses are very skillful at using their own proteins to evade the immune system. All viruses have mastered ways to do this, but HIV may be the champion."
Studies on similar vaccine strategies conducted in monkeys against the Simian AIDS virus have been carried out by Norman Letvin, M.D., and his colleagues in the Division of Viral Pathogenesis at BIDMC.
To learn more about participating in the trials, please call (617) 667-9925.
Beth Israel Deaconess Medical Center is a major patient care, research and teaching affiliate of Harvard Medical School and a founding member of CareGroup Healthcare System. Beth Israel Deaconess is the third largest recipient of National Institutes of Health research funding among independent U.S. teaching hospitals.