The National Institute of Allergy and Infectious Diseases (NIAID) announced today four novel public-private partnerships to accelerate development of promising HIV/AIDS vaccines for use around the world. The new partnerships, called HIV Vaccine Design and Development Teams (HVDDT), tap the different skills and talents of private industry and academic research centers, and provide incentive to move strong HIV/AIDS vaccine candidates out of the laboratory and into human testing. NIAID has committed to spend approximately $70 million over the next five years on the four HVDDT contracts that have been awarded.
The HVDDT program responds directly to President Clinton's call to increase public-private cooperation in developing vaccines against globally important diseases such as AIDS, tuberculosis and malaria.
"Many vaccines in use today resulted from both government-sponsored and private research," explains Anthony S. Fauci, M.D., director of NIAID. "The HVDDT program is a unique addition to this model that encourages the private sector to increase their AIDS vaccine efforts while allowing NIAID to work closely with its partners throughout the development process."
Designing and testing vaccines for diseases like AIDS is an expensive and scientifically complex undertaking with no guarantees of success and little likelihood of significant profit. "The HVDDT program encourages pharmaceutical companies to invest more in AIDS vaccine research by partially offsetting their financial risk. In essence, HVDDT contracts 'prime the pump' to get the vaccine-production engine running, including vaccine candidates for HIV subtypes that circulate in developing countries," explains Peggy Johnston, Ph.D., assistant director for AIDS vaccines at NIAID.
HVDDT awards are incentive-based contracts aimed at vaccine candidates in the middle of the development pipeline --those not yet in clinical testing. Applicants were required to describe a clear development plan, including timelines to indicate when different phases would be completed. Funding will be provided in increments as these preset milestones are reached. "This goal-based incentive structure helps ensure continuous progress toward a testable vaccine while at the same time rewarding companies for research accomplishments made along the way," states Dr. Johnston.
Each of the initial HVDDT contracts proposes using a DNA-based HIV vaccine for the initial immunization. The proposals differ in the unique properties of the DNA, the specific immune response that is targeted, the delivery system used, and the manner of boosting the initial vaccine. Each of the proposed vaccines contains the genetic information to make specific HIV proteins, either from the outer viral envelope or the internal viral core, to induce an immune response. The vaccines do not contain enough genetic information to construct a complete virus, and therefore will pose no threat of HIV infection to study participants. The four research organizations that have received an award and a summary of their proposed projects are listed below.
**ADVANCED BIOSCIENCE LABORATORIES, INC. (ABL), KENSINGTON, MD**
Under the direction of Phillip Markham, Ph.D., researchers from ABL and the University of Massachusetts Medical School will develop and test a DNA vaccine containing genes for envelope proteins from HIV strains isolated around the world. Study participants will receive non-DNA booster vaccines consisting of engineered, or recombinant, HIV proteins. The researchers will explore ways to enhance the antibody response to this vaccine and hope that this combination will provide broad immunity against the different subtypes of the virus found worldwide. ABL is an affiliate of Organon Teknika Corporation in Durham, NC.
**CHIRON CORPORATION, EMERYVILLE, CA**
Susan Barnett, Ph.D., and colleagues at Chiron will produce a DNA vaccine candidate based on a common U.S. HIV subtype called clade B. They will also work on a vaccine based on a clade C virus, the most common HIV subtype in sub-Saharan Africa and India. The vaccines, consisting of HIV envelope and core protein genes, are designed to stimulate antibodies and T cells that attack the virus and virus-infected cells, respectively. The DNA vaccine will be followed by a booster vaccine consisting of alphavirus particles, which serve as novel delivery vehicles to ferry a recombinant HIV protein to certain immune cells. By slightly changing the genetic code of the vaccine's DNA, Chiron scientists hope to improve the ability of the body to decode the genetic instructions once the vaccine is administered. The investigators will also study different ways to enhance the immune response to the DNA vaccine.
**UNIVERSITY OF NEW SOUTH WALES, AUSTRALIA**
David Cooper, M.D., will lead a consortium of Australian universities and research organizations in producing a DNA vaccine that contains HIV genes as well as specific stretches of DNA that directly stimulate immune responses. The vaccination boost will contain HIV genes contained in a viral (fowlpox) delivery system that also contains immunity-enhancing genes. This vaccine is designed to stimulate both antibody and T-cell responses and to generate active immunity at mucosal surfaces, the first site of viral assault during most HIV infections.
**WYETH LEDERLE VACCINES AND NUTRITION, PEARL RIVER, NY**
Wyeth Lederle's John Eldridge, Ph.D., will direct an effort with academic researchers at the University of Pennsylvania and Duke University to produce a DNA vaccine containing immunity-stimulating genes in addition to the HIV genes. The initial DNA vaccination will be boosted by a candidate vaccine consisting of multiple protein fragments, or peptides, that trigger anti-HIV responses. The goal of this approach is to produce a vaccine that strongly stimulates HIV-specific immune responses in very diverse human populations. The HVDDT awards are part of NIAID's expanded commitment to develop an HIV vaccine, and the contracts complement other currently supported HIV vaccine research and development programs. The Innovation Grant Program (IGP) supports novel, high-risk, and exploratory studies in AIDS vaccine-related research. The HIV Vaccine Research and Design Program (HIVRAD) supports studies emphasizing targeted AIDS vaccine research and development and is designed for vaccine concepts that have already generated significant preliminary data. The Integrated Preclinical/Clinical AIDS Vaccine Development Program (IPCAVD) supports grants designed to move promising HIV vaccine candidates into preliminary human studies. IPCAVD awards are not milestone-driven, however, because they support vaccine development at an earlier stage than the HVDDT contracts, where timelines are more difficult to predict. NIAID also supports HIV vaccine development through its Vaccine Development Resources program, which assists AIDS researchers by manufacturing pilot lots of vaccine for testing, conducting preliminary safety and efficacy evaluations, and preparing submissions to the Food and Drug Administration for trials in humans. More recently, NIAID announced the funding of the HIV Vaccine Trials Network (HVTN), a global network of clinical sites, which will conduct all phases of clinical trials of candidate HIV vaccines. NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illness such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.
For more information on NIAID's AIDS vaccine research program, please visit http://www.niaid.nih.gov/daids/vaccine/. Press releases, publications and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.