BETHESDA, MdThe National Institute of Allergy and Infectious
Diseases (NIAID) has formed four public-private partnerships aimed at
accelerating the development of promising HIV/AIDS vaccines.
In announcing the signing of the four contracts, NIAID said it has
committed about $70 million over the next 5 years to help support the
research.
The program, called HVDDT (HIV Vaccine Design and Development Teams),
is designed to tap the diverse research talents of industry and
academia, and provide incentives to move candidate vaccines out of
the laboratory and into human testing.
Many vaccines in use today resulted from both
government-sponsored and private research, said Anthony S.
Fauci, MD, 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 NIAID said in a news
release announcing the program.
Priming the Pump
The HVDDT program encourages pharmaceutical companies to invest
more in AIDS vaccine research by partially offsetting their financial
risk, said Peggy Johnston, PhD, the institutes assistant
director for AIDS vaccines. 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.
HVDDT awards are incentive-based contracts aimed at vaccine
candidates in the middle of the development pipelinethose 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, Dr.
Johnston said.
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 Contracts
The HVDDT contracts went to:
Advanced BioScience Laboratories, Inc., (ABL) Kensington,
Md. The company will work with University of Massachusetts
Medical School researchers to 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 recombinant HIV proteins. The researchers will explore ways to
enhance the antibody response to this vaccine. Principal investigator
is Phillip Markham, PhD. ABL is an affiliate of Organon Teknika
Corporation, Durham, NC.
Chiron Corp., Emeryville, California. Chiron
investigators will seek to produce a vaccine against an HIV subtype
commonly found in the United States called clade B, and another
against clade C, the most common subtype found in sub-Saharan Africa
and India.
The vaccines include the HIV envelope and core protein genes, and are
intended to stimulate antibodies against the virus as well as T cells
to attack virus-infected cells. The DNA vaccine will be followed by a
booster vaccine consisting of alphavirus particles that deliver a
recombinant HIV protein to certain immune cells.
By slightly changing the genetic code of the vaccines DNA,
Chiron scientists hope to improve the ability of the body to decode
the genetic instructions once the vaccine is administered. Principal
investigator is Susan Barnett, PhD.
University of New South Wales, Australia. David Cooper,
MD, will lead a consortium of Australian universities and research
organizations in the development of a DNA vaccine containing HIV
genes and specific stretches of DNA that directly stimulate immune
responses. The vaccination boost will contain HIV genes in a viral
(fowlpox) delivery system that also includes immunity-enhancing
genes.
The 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 researchers will work in collaboration with scientists at
the University of Pennsylvania and Duke University to produce a DNA
vaccine that contains HIV genes and genes that stimulate the immune
system. 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 stimulates
HIV-specific immune responses in very diverse human populations. The
team is led by Wyeth Lederles John Eldridge, PhD.
