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
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
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.