On April 21 and 22, a working group of the National Institute of Allergy and Infectious Diseases (NIAID) met to evaluate whether or not the current scientific data warrant expanding clinical trials of one or both candidate HIV vaccines that are furthest along development. Their evaluation supported advancing such trials.
The HIV Vaccine Working Group (VWG), formed by NIAID in December 1992, periodically reviews the status of HIV vaccine research to define what scientific questions are most important to advance the field and how the research community should address them. Current members include NIAID staff, other government and non-government scientists and community representatives committed to vaccine development. Ashley T. Haase, M.D., head of the department of microbiology at the University of Minnesota Medical School in Minneapolis, and Margaret Johnston, Ph.D., acting deputy director of NIAID's Division of AIDS (DAIDS), co- chaired the meeting.
The VWG's evaluation is just one step in the decision- making process to determine when and with what products NIAID will move into an expanded Phase II or Phase III HIV Vaccine efficacy trial. As he opened the meeting, Jack Killen, M.D., director of DAIDS, emphasized that the scientific rationale for expanding clinical trials must be considered along with other crucial factors that bear on this decision, including the readiness of potential trial sites, other vaccines in the pipeline, community concerns, legal and ethical issues and resources. "As a first step toward initiating large-scale vaccine trials, however, it is essential to develop a comprehensive understanding of the state of science," he said.
Both candidate vaccines evaluated by the VWG at the April meeting contain genetically engineered versions of the major HIV envelope protein, gp120. The vaccines are based on two different but closely related HIV-1 strains representative of most infections in North America and Europe. The Biocine Company (a joint venture of Chiron and CIBA-Geigy, Emeryville, California) made its vaccine from the SF-2 strain; Genentech, Inc. (South San Francisco) based its on the MN strain. Currently, these are the only experimental HIV vaccines being evaluated in a Phase II NIAID-sponsored preventive vaccine clinical trial. NIAID began the trial in its five national AIDS Vaccine Evaluation Units in December 1992.
At the meeting, scientists from Biocine and Genentech presented summaries of published and unpublished laboratory, animal model and clinical trial information. This information included preliminary but encouraging results from studies in which chimpanzees were vaccinated and then challenged with HIV. The companies organized their presentations according to NIAID guidelines regarding the scientific data the Institute deem important for facilitating the efficacy trial decision-making process.
Other speakers addressed additional considerations including the history of vaccine development decisions in the United States, preparedness of potential HIV vaccine sites, protective immune responses against HIV, HIV diversity, primate and other animal model data, Phase I and Phase II clinical trials and specific concerns of volunteer communities.
After considering the companies' data within this larger context, the vast majority of the VWG agreed that additional laboratory or animal model data are unlikely to add significantly to the knowledge base that would predict whether or not a recombinant gp120 candidate vaccine might afford protection from HIV infection. They concluded that the scientific rationale supports advancing and expanding clinical trials to evaluate this hypothesis further. Such trials would be incorporated into a broader prevention effort and would include frequent counseling of trial volunteers on how to avoid HIV infection.
The objectives and design of these expanded studies will be worked out by the NIAID staff within the next six to seven weeks with input from all parties concerned, including the VWG, the companies and the Food and Drug Administration. NIAID in collaboration with the Centers For Disease Control and Prevention and the National Institute on Drug Abuse currently sponsors research on the feasibility of conducting large HIV vaccine trials in high-risk communities around the country. Data from these studies will be factored into NIAID's assessment.
In mid-June, DAIDs staff will present their evaluation and a proposed trial design to NIAID's AIDS Research Advisory Committee (ARAC) and the AIDS subcommittee of the Institute's Advisory Council. ARAC is the primary advisory group to NIAID on the research program of DAIDS. ARAC members represent a wider variety of AIDS research and patient concerns than the VWG and can provide a broader perspective on expanding clinical testing of these vaccines. Following this meeting, ARAC will submit its recommendation to Anthony S. Fauci, M.D., NIAID director, who will then decide how to proceed.
The clinical evaluation of other experimental products remains an essential component of NIAID's mission to facilitate research on developing an effective AIDS vaccine. NIAID will continue to monitor and re-evaluate the state-of- the-art in HIV vaccine development and consider moving other candidate vaccines into expanded clinical studies as more information on them becomes available. Significant development concerning any viable preventive approach may lead to appropriate changes in the direction or scope of NIAID's commitment to a specific candidate HIV vaccine or alternative preventive strategy.
NIAID's current priorities and activities for basic, preclinical and clinical research on HIV vaccines are outlined in its HIV/AIDS Research Agenda. A copy of this report can be requested from DAIDS by calling 301-496-0545.
NIAID, a component of the National Institute of Health, supports research on AIDS, tuberculosis and other infectious diseases in addition to allergies, immunology and transplantation. NIH is an agency of the U.S. Public Health Service, U.S. Department of Health and Human Services.Prepared by: