Dr. Rabinovich presented highlights of the NIAID vaccine research program, with emphasis on its diversity; pointed to some recent successes, and described the approaches to defining priorities and accomplishing goals.

The NIAID program cross-cuts the Institute, with research projects related to vaccines against more than 30 diseases. For example, in the 1970's, the Institute undertook support of projects on Haemophilus influenzae type b, the leading cause of bacterial meningitis in children, extending earlier finding on the etiology of meningitis and the protective role of antibodies, leading to the clinical trial in Finland that demonstrated the polysaccharide vaccine was effective in older children but ineffective in younger children. Similar efforts have supported research and development of live attenuated varicella vaccine, acellular pertussis and, arising from the Intramural Laboratory for Infectious Diseases, rotavirus vaccines.

The total NIH support for vaccine research in FY 1996 is approximately $312 Million. As a cross-NIH scientific area of interest, other institutes, notably NCI, NCRR and NICHD also have commitments in this area. NIAID remains the lead Institute, with an estimated FY 1996 budget of $196,971 total, with $105 Million dedicated for vaccines against infectious diseases other than HIV AIDS.

The DMID program for vaccine research, developed on the basis of long term initiatives in acellular pertussis and Hib, arises from a strong foundation of basic research. A number of steps must be reached and barriers overcome, and working collaboratively with investigators, the FDA, and vaccine companies, the NIAID has established a number of mechanisms to accelerate this process for vaccine of public health importance, including animal models, pilot lot production, vaccine evaluation, regulatory affairs and collaborations with industry. Over 30 target diseases of public health importance are part of the DMID program.

The Institute of Medicine reports commissioned by the NIAID, published in 1985 and 1986, defined priorities vaccines for development. In 1993, NIAID convened a Blue Ribbon Panel to assess long-term goals for vaccine research as well as recommend priorities for use of additional resources in FY 1993 and 1994. The process continues with the NIH-supported project with the IOM evaluate vaccine research priorities for the 21st century. The project will be completed early in 1997.

The future of the DMID vaccine research program will continue to be based on a strong foundation of investigator-initiated research in the areas of microbiology, immunology and vaccinology. This will be augmented by the continued search for and evaluation of novel approaches to vaccines, such as DNA vaccines, transgenic plants, and vaccine vectors; preclinical and clinical evaluation in dedicated, multi-disciplinary centers such as the Vaccine and Treatment Evaluation Units and Mucosal Pathogen Research Units. Using available mechanisms, including CRADAs, SBIRs and STTR, the DMID will extend collaborations to interested groups for vaccines of public health importance.

A vaccine to prevent HIV infection and/or disease is a major goal of the NIAID. Much has been learned about HIV vaccines in the last decade. However, proof that a particular candidate vaccine will prevent HIV infection or AIDS is still at best, several years away. This presentation summarized both the Institute's current knowledge of HIV vaccines as well as where the NIAID is going with its vaccine strategy.

We now know that the human immune response partially suppresses HIV replication and postpones clinical disease in most infected individuals for about a decade. Data from nonhuman primate models suggest that vaccine-induced immunity can either prevent HIV infection or control disease progression. A variety of vaccine approaches are being explored in the laboratory and in early clinical trials; they have proved safe, but their ability to induce immune responses varies. Attempts to locate populations in which larger-scale efficacy tests of HIV vaccine can be conducted, i.e., cohorts that can be recruited and followed, who still are at some risk despite best efforts at education and counseling, and who want to participate in trials have met with considerable success both in the United States and internationally.

The overall NIAID strategy is to balance support for strong basic research on the biology and pathogenesis of HIV and human immunology with a targeted approach to vaccine research and development. A major component of the strategy has been the development of formal collaborations with vaccine manufacturers. This strategy has evolved over time based on research into the ability of HIV to continually change both within the body of each infected individual and about the ability of any one vaccine, or even a vaccine cocktail, to raise humoral antibody responses against the HIV envelope that are sufficiently strong and broad to protect against the varied HIV strains an individual may encounter.

The NIAID-supported AIDS Vaccine Evaluation Group (AVEG) has studied 23 vaccines or regimens to date. Based on preclinical as well as AVEG data, the prime-boost combination of ALVAC-gp120 is now being studied in late Phase 1 trials; a Phase II trial is planned for early next year, and if data warrant, an efficacy trial could begin in 1998. Thus, the NIAID strategy has resulted in an unconventional prime-boost vaccine approach that can engage both T-cell and antibody responses to the greatest extent now possible in human beings. This strategy will continue to move the Institute toward its goal of an effective HIV vaccine.