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CLINICAL TRIALS Trials Open at HMS to Test HIV VaccineThe first Harvard study of a vaccine to protect against HIV in human volunteers began this month as part of an NIH-sponsored global network aimed at moving preventive vaccines from the lab through clinical trials.
The staff of Harvard Medical School's HIV vaccine unit study site at Brigham and Women's Hospital. These physicians, nurses, technicians, and administrators are members of a team conducting the first clinical trial at HMS to test a vaccine to prevent infection with the AIDS virus. Left to right: Lindsey Baden, Kristin Schwab, Kristen Brady, Spyros Kalams, Elvira Dragileva, Raphael Dolin, Shahin Lockman, Roger Shapiro, John Abbatematteo, Kathleen Neill, and Raphael Landovitz. Photo by Jeff Cleary Based at HMS, the new HIV Vaccine Clinical Trial Unit is a collaborative effort among HMS, HSPH, Boston's Fenway Community Health Center, and Brown University in Providence. The studies will be conducted at the Clinical Trials Center at Brigham and Women's Hospital, the Fenway center, and Miriam Hospital in Providence. HSPH investigators will direct an overseas site in Botswana which, along with neighboring Zimbabwe, has the world's highest HIV infection rate. Funded by a 5-year, $12 million grant from the National Institute of Allergy and Infectious Diseases, the unit is one of 10 in a vaccine trials network set up by NIAID in 1999. Other units in the network have study sites in South Africa, China, Thailand, India, Peru, Brazil, Haiti, Trinidad and Tobago, and across the U.S. Fazing HIVInitially, the HMS unit will conduct phase I and II trials to assess vaccine safety and immunogenic activity. The target is to enroll 100 volunteers in phase I and 50 in phase II trials in the first year. The grant also covers planning for phase III efficacy trials."The purpose is to take the most promising vaccine approaches developed anywhere in the world and translate them very rapidly into studies in humans, with the idea that the most promising of those would, in turn, be taken into efficacy trials," said Raphael Dolin, dean for clinical programs and the unit's principal investigator. Early human trials involve escalating the vaccine dose and measuring immune response to see whether the vaccine raises the levels of cell-mediated or humoral immunity that might prevent infection, or suppress viral levels if infection does occur. Although HIV preventive vaccines are new to HMS as an institution, the unit's leaders have broad experience in the field. Dolin founded and directed the AIDS vaccine evaluation unit at the University of Rochester before coming to HMS in 1998. The ExpertsSpyros Kalams, assistant professor of medicine at Massachusetts General Hospital and an expert in HIV immunotherapy and prophylaxis, is a co-investigator of the unit, and Lindsey Baden, instructor in medicine at BWH, serves as clinical director of the site there. Ken Mayer is clinical director of the Fenway and Brown sites, where he took part in prior HIV vaccine trials sponsored by HIVNET, the precursor of the current network. Bruce Walker, professor of medicine at MGH and a leading researcher in HIV immune responses, is also a co-investigator for the study. And Max Essex, chair of the Harvard AIDS Institute and the Lasker professor of health sciences at HSPH, will direct activities at the Botswana site. Dolin and Walker also serve in leadership positions in the vaccine trial network.The unit's first study is a network-wide phase II trial of a canarypox vector vaccine with a gp120 protein, the vaccine that is furthest along. Dolin noted, "We are particularly interested in trials of vaccines that have been developed in laboratory and animal studies done by our faculty at Harvard." A DNA vaccine augmented with an IL-2/Ig protein, developed and studied in rhesus monkeys by Norman Letvin of Beth Israel Deaconess Medical Center and Dan Barouch of MGH (see Focus, April 21, 2000), will be the first such "homegrown" vaccine, which Dolin said is expected to go into a trial later this year. In addition to the clinical trials, the vaccine unit also interacts with basic science "research emphasis groups" to foster collaboration between basic and clinical scientists interested in HIV vaccines. These include the labs of Walker and Letvin as well as Joseph Sodroski, professor of pathology at the Dana–Farber Cancer Institute, and Marian Neutra, the Ellen and Melvin Gordon professor of pediatrics at Children's Hospital. The unit also has community advisory boards in Boston and Providence that work with the investigators on recruitment, education, and scientific and ethical issues. —Tom Reynolds |
