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SEATTLE -- The Bill & Melinda Gates Foundation today
announced 16 grants totaling $287 million to create an
international network of highly collaborative research
consortia focused on accelerating the pace of HIV vaccine
development.

The grants will support a range of innovative approaches for
designing an effective HIV vaccine, and bring together more
than 165 investigators from 19 countries to tackle some of the
biggest scientific challenges facing the field.

Eleven consortia will focus on vaccine discovery, applying
new scientific knowledge and cutting-edge research techniques
to create and evaluate novel vaccine candidates. These
consortia will be linked to five central laboratories and data
analysis facilities, enabling investigators to openly share
data and compare results, and allowing the most promising
vaccine approaches to be quickly prioritized for further
development.

"An HIV vaccine is our best long-term hope for controlling
the global AIDS epidemic, but it has proven to be a
tremendously difficult scientific challenge," said Dr. José
Esparza, senior advisor on HIV vaccines for the Gates
Foundation. "We have all been frustrated by the slow pace of
progress in HIV vaccine development, yet breakthroughs are
achievable if we aggressively pursue scientific leads and work
together in new ways."

To date, most HIV vaccine research has been conducted by
small teams of investigators working independently. While
important research gains have been made, there is growing
recognition that these efforts need to be supported by new
large-scale, collaborative projects that can produce definitive
answers to complex scientific questions.

Grants Establish Vaccine Discovery Consortia, Central
Facilities

The grants announced today, known collectively as the
Collaboration for AIDS Vaccine Discovery, will support the
following:

• Vaccine discovery consortia: Eleven vaccine discovery
consortia will pursue a broad range of innovative strategies
for designing vaccine candidates to trigger immune responses
believed to be critical for protection against HIV.

The consortia will focus on overcoming two of the biggest
scientific obstacles currently facing the field: designing
vaccine candidates capable of eliciting effective neutralizing
antibodies to HIV, and improving current vaccine candidates so
they elicit stronger and more durable protective cellular
immune responses.

• Central facilities: Five central facilities will be
established, including three laboratory networks for measuring
the immune responses elicited by vaccine candidates, a research
specimen repository, and a data and statistical management
center.

As a condition for receiving funding, the newly-funded
vaccine discovery consortia have agreed to use the central
facilities to test vaccine candidates, share information with
other investigators, and compare results using standardized
benchmarks.

"These projects bring a new level of creativity and
intensity to bear on major scientific challenges facing HIV
vaccine development," said Dr. Nicholas Hellmann, acting
director of the Gates Foundation's HIV, TB, and Reproductive
Health program. "Some of the vaccine concepts that will be
pursued have been talked about for years, but have never been
adequately studied. If successful, they could lead to entirely
new paradigms for HIV vaccine development."

"These grants signal an exciting move toward greater
cooperation, coordination, and transparency among vaccine
scientists," said Mitchell Warren, executive director of the
AIDS Vaccine Advocacy Coalition (AVAC). "AIDS vaccine advocates
have long said that this type of work is critical to
accelerating work in the field, and this is an energizing
time."

In addition, the grantees are developing global access plans
to help ensure that their discoveries will be accessible and
affordable for developing countries, where the vast majority of
new HIV infections occur.

Range of Novel HIV Vaccine Approaches Supported

The grants announced today support a range of novel
approaches for developing an effective HIV vaccine. (See
accompanying backgrounder for grant details.) Examples of the
grants include:

• Advancing progress on neutralizing antibodies: Virtually
all licensed vaccines for other diseases are believed to work
by causing the immune system to produce neutralizing antibodies
that bind to vulnerable regions on the infection-causing agent.
One research consortium will isolate a large number of
antibodies from humans and animals, screen them for the ability
to neutralize HIV, and "work backwards" from the best
antibodies to design new vaccine candidates. (Lead
investigator: Robin Weiss, University College London)

• Using computational biology to create novel vaccine
designs: One research consortium will use state-of-the-art
computer design techniques to create synthetic molecules to
trigger antibodies against HIV. To help provide the massive
computing power necessary for this project, the consortium will
partner with the Rosetta@home project, which allows individuals
around the world to donate their personal computer's idle time
to run research calculations over the Internet. (Lead
investigator: Leo Stamatatos, Seattle Biomedical Research
Institute)

• Addressing challenges in eliciting cellular immunity: An
effective HIV vaccine may also need to elicit cellular, or
T-cell, immunity. One potential approach for eliciting cellular
immunity is to modify other viruses so they carry pieces of HIV
capable of inducing an immune response (but not capable of
causing disease). One research consortium will focus on a
number of novel vectors, or "carrier" viruses, that have been
identified as promising for an HIV vaccine but have never been
tested in clinical trials. (Lead investigator: Timothy Zamb,
International AIDS Vaccine Initiative)

• Improving vectors that elicit cellular immunity: The use
of poxviruses as vaccine vectors is supported by extensive
pre-clinical and clinical experience, and one of the projects
will try to significantly improve the ability of poxvirus
vectors to stimulate cellular immune responses. The consortium
will focus on making improvements to three poxvirus vectors
that have been used in HIV vaccines, including a modified
version of the vaccinia virus that was successfully used to
eradicate smallpox. (Lead investigator: Giuseppe Pantaleo,
Centre Hospitalier Universitaire Vaudois)

• Harnessing dendritic cells: The immune system's dendritic
cells are believed to play an important role in enhancing both
cellular immunity and neutralizing antibodies. One research
consortium will design vaccine candidates with molecules that
bind to the surface of dendritic cells, and study the use of
chemicals called glycolipids, which activate immune cells that
stimulate dendritic cells. (Lead investigator: David Ho, Aaron
Diamond AIDS Research Center, The Rockefeller University)

• Standardizing and improving laboratory tests: Laboratory
tests used to assess vaccine candidates are often not
comparable due to variations in techniques and materials,
severely hampering decisions about which candidates to pursue
for further testing. One grant will establish an international
network of laboratories to standardize procedures for
evaluating neutralizing antibody responses elicited by HIV
vaccine candidates. (Lead investigator: David Montefiori, Duke
University)

In total, the 16 grants support more than 165 investigators
in 19 countries: Australia, Austria, Belgium, Cameroon, Canada,
Denmark, France, Germany, India, Japan, the Netherlands, South
Africa, Spain, Sweden, Switzerland, Uganda, the United Kingdom,
the United States, and Zambia.

Grants Address Key Research Gaps Identified by Global HIV
Vaccine Enterprise; Additional Funding Still Needed

The Gates Foundation grants help address research priorities
identified by the Global HIV Vaccine Enterprise, an alliance of
researchers, funders, and advocates from academia, governmental
and non-governmental organizations, and private industry in
developing and developed countries dedicated to implementing a
shared scientific plan to accelerate HIV vaccine development.
The Enterprise's scientific plan prioritizes vaccine discovery
and laboratory standardization as two of the top issues facing
the vaccine field.

The foundation grants complement other contributions in
support of the Enterprise scientific plan, including:

• Switzerland: The Government of Switzerland has pledged to
support the establishment of a vaccine institute in Lausanne
that will contribute to the implementation of the Enterprise
scientific plan.

• Germany: The Fraunhofer Society and the Ministry of
Economic Affairs of Saarland in Germany have committed a total
of $1.7 million to support the Enterprise scientific plan.

• U.S.: Last year the U.S. National Institute of Allergy and
Infectious Diseases (NIAID) pledged more than $300 million to
support the Center for HIV/AIDS Vaccine Immunology (CHAVI),
which is addressing other priorities in the Enterprise
plan.

Yet resources for HIV vaccine development still fall
significantly short of need. According to an analysis
co-sponsored by the AVAC, International AIDS Vaccine
Initiative, UNAIDS, and other groups, an estimated $682 million
is spent annually on HIV vaccine development, while fully
implementing the Enterprise scientific plan would require
nearly double this amount – an estimated $1.2 billion
annually.

"The Global HIV Vaccine Enterprise provides a forum for
researchers and donors to work together on one of the most
important challenges of our time," said Dr. Mark Walport,
director of the Wellcome Trust and a member of the Enterprise
Coordinating Committee. "By clearly identifying funding gaps,
the Enterprise is helping donors ensure that resources are used
most effectively."

Other priorities in the Enterprise scientific plan include
developing improved vaccine manufacturing processes,
establishing greater clinical trials capacity in developing
countries, improving regulatory capacity for approving clinical
trials and assessing trial results, and developing intellectual
property arrangements that facilitate global access to new
technologies.

"As researchers make progress in designing promising new
vaccine candidates, it is essential that sufficient capacity is
in place to manufacture these vaccines, test them in clinical
trials, and conduct timely reviews of the results," said Dr.
Barton Haynes, professor of medicine at Duke University Medical
Center who is principal investigator of NIAID's CHAVI, and also
the lead investigator on one of the Gates Foundation grants
announced today. "The grants funded by the Gates Foundation
will complement the efforts of CHAVI."