Margaret I. Johnston, Ph.D., acting deputy director of the Division of AIDS of the National Institute of Allergy and Infectious Diseases (NIAID), will present a state-of-the-art lecture on progress in HIV vaccine research and development on Wednesday, Feb. 1, 1995, at the Second National Conference on Human Retroviruses and Related Infections in Washington, D.C.
A vaccine for AIDS is possible, but researchers face a special combination of scientific challenges that will require the integration of two strategic approaches, including the simultaneous evaluation of different vaccine concepts, and a strong and diverse basic research effort, says Dr. Johnston. These challenges include the enormous genetic diversity of HIV, the lack of an ideal animal model of HIV disease and the absence of a verified state of natural immunity.
A rational overall strategy for HIV vaccine development should evaluate the safety, immunogenicity and potential efficacy of a range of promising vaccine concepts in animal models and human Phase I and Phase II trials. Ultimately, the effectiveness of only the most promising concepts should be determined in expanded trials in appropriate uninfected populations at higher risk for HIV infection.
Dr. Johnston will provide a summary of current data on recombinant vaccines based on HIV's gp120 envelope protein and then focus on other vaccines in or near clinical development, including pox virus vectors expressing multiple HIV genes and peptide-based approaches. Phase I trials testing improved designs of these and other vaccine concepts could start in the United States in 1995 or 1996, she says, and Phase II human testing in 1996 or 1997.
Novel vaccine concepts being explored in the laboratory and animal studies include DNA vaccines, HIV-like particles and subunit combinations, which could enter Phase I testing soon, according to Dr. Johnston.
The second strategic component includes a concerted effort in basic research targeted toward a number of obstacles facing vaccine developers. Dr. Johnston will summarize the knowledge base and immediate priorities in four critical areas:
1) Correlates of immunity, to better define the immune responses desired from an HIV vaccine. For example, scientists should intensively study animal models, vaccine trial volunteers who become infected, HIV-infected people who remain healthy for many years without losing immune function, and those exposed to HIV who resist infection.
2) Animal model development, to identify the best animal model(s) in which to test vaccine concepts. Investigators should more thoroughly examine the dynamics and course of infection in various animal models to identify those which most closely parallel human disease.
3) HIV diversity, to understand and overcome the problems posed by HIV's genetic variability. Researchers need to develop better assay systems, examine the immunologic significance of genetic diversity, and design approaches to overcome diversity.
4) Behavioral research, to prepare for efficacy trials. For example, scientists should continue to study barriers to participation in trials, and develop and validate measures of risk-taking behavior and behavioral change. These studies are essential to the design of successful large-scale field trials.
NIAID, part of the National Institutes of Health, supports research aimed at preventing, diagnosing and treating such illnesses as AIDS, tuberculosis and asthma as well as allergies. NIH is an agency of the U.S. Public Health Service, part of the U.S. Department of Health and Human Services.