[Senate Prints 109-44]
[From the U.S. Government Publishing Office]
109th Congress S. Prt.
COMMITTEE PRINT
1st Session 109-44
_______________________________________________________________________
2005 AIDS VACCINE INTERNATIONAL
CONFERENCE, MONTREAL, CANADA,
SEPTEMBER 6-9, 2005
__________
STAFF TRIP REPORT
TO THE
COMMITTEE ON FOREIGN RELATIONS
UNITED STATES SENATE
One Hundred Ninth Congress
First Session
December 2005
U.S. GOVERNMENT PRINTING OFFICE
25-334 WASHINGTON : 2005
_____________________________________________________________________________
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COMMITTEE ON FOREIGN RELATIONS
RICHARD G. LUGAR, Indiana, Chairman
CHUCK HAGEL, Nebraska JOSEPH R. BIDEN, Jr., Delaware
LINCOLN CHAFEE, Rhode Island PAUL S. SARBANES, Maryland
GEORGE ALLEN, Virginia CHRISTOPHER J. DODD, Connecticut
NORM COLEMAN, Minnesota JOHN F. KERRY, Massachusetts
GEORGE V. VOINOVICH, Ohio RUSSELL D. FEINGOLD, Wisconsin
LAMAR ALEXANDER, Tennessee BARBARA BOXER, California
JOHN E. SUNUNU, New Hampshire BILL NELSON, Florida
LISA MURKOWSKI, Alaska BARACK OBAMA, Illinois
MEL MARTINEZ, Florida
Kenneth A. Myers, Jr., Staff Director
Antony J. Blinken, Democratic Staff Director
(ii)
C O N T E N T S
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Page
Letter of Transmittal............................................ v
Conference Overview.............................................. 1
Scientific Challenges to Developing an Effective HIV Vaccine. 1
Efforts to Coordinate AIDS Vaccine Research.................. 3
Other Challenges in the Pursuit of an Effective AIDS Vaccine. 3
Concluding Thoughts and Recommendations.......................... 6
(iii)
LETTER OF TRANSMITTAL
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December 28, 2005
Hon. Richard G. Lugar, Chairman,
U.S. Senate Committee on Foreign Relations.
Dear Senator Lugar:
On behalf of the Senate Committee on Foreign Relations, I
traveled to Montreal, Canada from September 6-9, 2005. The
purpose of this trip was to attend the 2005 AIDS Vaccine
International Conference.
The trip afforded me the opportunity to learn about the
latest scientific progress in developing an AIDS vaccine,
better understand the myriad social issues surrounding this
work, and consult with key individuals working on this issue.
Attached is a summary of the trip and a discussion of the
impressions and conclusions developed throughout the trip. The
conclusions in this report are my own and do not necessarily
reflect the views of the Committee on Foreign Relations or its
members.
Sincerely,
Chris Ann Keehner,
Counsel, Majority Staff,
U.S. Senate Committee on Foreign Relations.
(v)
2005 AIDS VACCINE INTERNATIONAL
CONFERENCE, MONTREAL, CANADA,
SEPTEMBER 6-9, 2005
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Conference Overview
Despite the dramatic increase in funding in the last few
years for programs to prevent the spread of the human
immunodeficiency virus (``HIV'') and to treat those living with
the acquired immune deficiency syndrome (``AIDS''), the spread
of the disease continues to outpace us. According to UNAIDS,
there are an estimated 40.3 million people living with HIV
today. Over three million people died of AIDS in 2005, and
nearly 4.9 million people became infected with HIV this year.
This means that every day around the globe, some 14,000 people
are newly infected with HIV. In addition, experts are concerned
about a possible ``second wave'' of countries with AIDS
epidemics, including Russia, China, India, Nigeria, and
Ethiopia.\1\
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\1\ For more information on the current state of the AIDS pandemic,
see the UNAIDS/WHO AIDS Epidemic Update: December 2005, which can be
found at http://www.unaids.org.
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Getting ahead of this pandemic--through current prevention
and treatment programs alone--will continue to be a challenge.
An effective AIDS vaccine holds promise to be the world's best
chance to stop this pandemic. Historically, vaccines have led
to some of the greatest achievements in public health and are
among the most cost-effective health interventions. During the
20th century, global immunization efforts have successfully led
to the eradication of smallpox and the elimination of polio
from the Western Hemisphere, Europe, and most of Asia. Vaccines
for diseases such as measles and tetanus have dramatically
reduced childhood mortality worldwide, and vaccines for
diseases such as influenza, pneumonia, and hepatitis now help
prevent the sickness and death of adults, too.
The theme of the 2005 AIDS Vaccine International Conference
was ``Together, A Better Future for All,'' and was held in
Montreal, Canada. The Conference brought together scientists,
policy makers, and activists from around the world with a
special interest in the development of vaccines to prevent HIV
and AIDS. The Conference provided a unique opportunity to learn
about the most recent scientific progress in developing an AIDS
vaccine and the social, ethical, and economic issues
surrounding the pursuit of this goal.
SCIENTIFIC CHALLENGES TO DEVELOPING AN EFFECTIVE HIV VACCINE
There are currently about 30 candidate AIDS vaccines in
clinical testing around the world today. The immediate goal of
AIDS vaccine research is to design candidate vaccines that
trigger responses from both the major arms of the body's immune
system--humoral immunity and cellular immunity. Humoral
immunity involves the creation of antibodies that recognize and
attack a pathogen--like HIV--in the blood and prevent it from
infecting the body's cells. Cellular immunity is triggered once
the pathogen has infected some of the body's cells, and its
role is to recognize and destroy infected cells to prevent
further spread of the pathogen.\2\
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\2\ For a more in-depth discussion of immunology and vaccine
development with respect to an AIDS vaccine, see the AIDS Vaccine
Advocacy Coalition's (AVAC) AIDS Vaccine Handbook (2d ed. 2005). The
full text of the book is available online at http://www.avac.org.
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The complicated nature of HIV, however, creates significant
scientific challenges for researchers. One of these challenges
is the way HIV interacts with the human immune system. Most
vaccines work by triggering the body's immune system to produce
antibodies against infection. The antibodies search out
invaders in the bloodstream--like viruses or bacteria--and
attack them. HIV, however, is extremely adept at evading the
immune system, thus making this approach to an AIDS vaccine
especially challenging. Determining how to design vaccines that
stimulate an antibody-producing response is a priority for
scientists. If a vaccine were able to produce this response, it
would block HIV infection altogether. Although most researchers
agree that solving this problem is essential to developing an
AIDS vaccine, so far, trials have been unsuccessful in creating
an antibody response.
Because of the difficulty in discovering a vaccine that
triggers an antibody-producing effect, most of the current
trials focus on cellular immunity, which if successful, might
not prevent an individual from getting HIV, but would delay or
prevent the progression of the disease and reduce transmission.
Researchers are closely watching the clinical trials of Merck &
Company, which has initiated a candidate aimed at stimulating
cellular immunity. This ongoing study is testing the company's
lead vaccine candidate known as ``MRKAd5'' in approximately
3,000 volunteers. This trial will test the hypothesis that a
vaccine based on portions of genetic material from HIV can
stimulate cellular immunity to prevent HIV disease, and perhaps
infection. This trial is being conducted in sites in the United
States, Australia, the Caribbean, and Latin America. The
results of this important trial are anticipated in 2007 at the
earliest, and will likely shape the direction of future AIDS
vaccine research.
Another complicating factor is HIV's diversity. There are
several strains of HIV and the virus is constantly generating
new ones. Globally, six different strains account for the
majority of HIV infections. This means that scientists need to
find vaccines that induce immunity against the broadest range
of these HIV strains.
Given the scientific challenges of developing an effective
HIV vaccine, researchers in the field are modifying the
traditional vaccine development process. Normally, clinical
trials are conducted in three phases. Phase I trials typically
involve several dozen volunteers at low risk for HIV infection
and test whether the vaccine triggers an immune response. Phase
II trials involve several hundred volunteers, including some at
high risk for HIV infection, and gather both safety and
immunogenicity\3\ data. Phase III efficacy trials enroll
thousands of participants and seek statistical determinations
of whether a vaccine is effective. Very few of the vaccines
tested will make it to Phase III testing. Although there have
been dozens of different AIDS vaccines tested in Phase I
trials, only three have made it into Phase III. Because of the
high cost in taking a vaccine all the way to Phase III trials,
AIDS vaccine developers have added a fourth phase to the
process: Phase IIb or ``proof of concept'' trials. The goal
behind this new phase is to look for preliminary evidence of
efficacy in smaller, shorter, and far less expensive trials
before engaging in a Phase III trial. (The Merck trial studying
cellular immunity is a Phase IIb trial.)
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\3\ When collecting data on immunogenicity, researchers are
examining the strength and breadth of the immune response of a trial
vaccine.
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EFFORTS TO COORDINATE AIDS VACCINE RESEARCH
Because of the complicated nature of AIDS vaccine research,
most experts agree that there is a need for a much larger-
scaled, better-coordinated, better-funded effort, consisting of
researchers from different organizations working together to
solve given scientific problems. Ideally, each of these
organizations would contribute its special expertise and would
share the information it discovers. Speakers at the Conference
discussed how efforts to better coordinate AIDS vaccine
initiatives have improved significantly over the past two
years. For instance, the Global HIV Vaccine Enterprise
(``Enterprise''), which was first proposed in Science magazine
in June 2003 and established in 2004, is a ``virtual
consortium'' of scientists, advocates, and other stakeholders
organized to accelerate research efforts to develop an AIDS
vaccine. In February 2005, the Enterprise published the
Scientific Strategic Plan, a blueprint outlining the major
scientific hurdles to be overcome in the development of an AIDS
vaccine.\4\ The Enterprise's first Stakeholders' Forum was held
in London on May 23-24, 2005, organized by the U.K. Department
for International Development and the Bill & Melinda Gates
Foundation. In October, the Enterprise held its first Funders'
Forum. Currently, the Bill and Melinda Gates Foundation is
acting as interim Secretariat, and the Enterprise is in the
process of selecting an Executive Director.
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\4\ For more information on the Global HIV Vaccine Enterprise, see
http://www.hivvaccineenter-prise.org.
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On the domestic front, Dr. Anthony S. Fauci, Director of
the National Institute of Allergy and Infectious Diseases at
the National Institutes of Health, spoke at the Conference
about the Partnership for AIDS Vaccine Evaluation (``PAVE''),
the interagency group coordinating AIDS vaccine research among
the Department of Defense, the Centers for Disease Control, the
National Institute of Allergy and Infectious Diseases, and
other agencies and offices. In addition, the Center for HIV/
AIDS Vaccine Immunology (``CHAVI'') was established by
President Bush last year, and is a consortium of universities
and academic medical centers organized by the National
Institute of Allergy and Infectious Diseases (NIAID) under Dr.
Barton Haynes of Duke University. It is intended to solve major
problems in AIDS vaccine development and to be a component of
the Global HIV Vaccine Enterprise.\5\ The CHAVI has received a
seven-year grant of $300 million for AIDS vaccine research and
plans on holding its first clinical trials in 2007. In addition
to federal funding for AIDS vaccine research, the Bill and
Melinda Gates Foundation has allocated $360 million for grants
in the context of the scientific plan of the Global HIV Vaccine
Enterprise.
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\5\ For more information on the CHAVI, see http://www.chavi.org.
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OTHER CHALLENGES IN THE PURSUIT OF AN EFFECTIVE AIDS VACCINE
Apart from the scientific challenges researchers face in
developing an effective AIDS vaccine, there are several other
issues that create tremendous hurdles in this field.
Increasing Private Sector Investment in AIDS Vaccine Research
One of the biggest challenges is the lack of private sector
investment in research and development of an AIDS vaccine.
There are two main reasons for this. First, many pharmaceutical
companies have ceased to invest in research and development of
vaccines, due to the liability risks involved and the lower
profit margin of vaccines compared to medicines taken to treat
chronic illnesses. Representatives of the private sector spoke
at the Conference about the tremendous costs involved in
bringing a product to market, and explained that most
medications are far more profitable than vaccines, which are
typically administered only once. Second, when the target
population for a new product, such as an AIDS vaccine, lives
largely in the developing world, there is essentially is no
viable commercial market to entice research and development in
the production of the product.\6\
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\6\ For a more thorough discussion of the challenges faced in
encouraging increased private sector research and development for
vaccines for diseases endemic to developing countries, see Making
Markets for Vaccines: Ideas to Action, by Ruth Levine, Michael Kremer,
and Alice Albright of the Center for Global Development. This report
can be accessed at http://www.cgdev.org.
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In order to fill this economic gap, experts are developing
various incentives to motivate the private sector to invest in
research and development for vaccines to prevent diseases, like
HIV, that are predominately found in the developing world.
Among these incentives are tax credits, ``wild card'' patent
extensions, and advanced market commitments. Public-private
partnerships have also proved beneficial in the pursuit of
vaccines for diseases of developing countries, and experts are
seeking ways to increase these partnerships.\7\
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\7\ In September, Senators John Kerry (D-MA) and Richard Lugar (R-
IN) introduced the Vaccines for the New Millennium Act of 2005, a bill
that seeks to accelerate efforts to develop vaccines for HIV/AIDS,
tuberculosis, malaria and other diseases in developing countries.
Representative Pete Visclosky (D-IN) introduced companion legislation
in the House of Representatives. See S. 1698 and H.R. 3781.
The Challenges of Conducting Vaccine Trials in Developing
Countries
Because the majority of people with HIV and AIDS live in
developing countries, it is essential that vaccine trials be
conducted in these countries to ensure an effective vaccine.
Conducting vaccine trials in underdeveloped countries, however,
is especially challenging for a variety of reasons. The biggest
challenge to conducting trials in these countries is the lack
of health care infrastructure and trained personnel. In
addition, in order for trials to be successfully carried out
and understood by volunteers participating in them, there is a
need for political leadership supporting the trials, and for
countries to develop national AIDS vaccine plans. Finally,
volunteers participating in vaccine trials need access to
treatment and counseling programs, and to the extent possible,
these trials should be coordinated with such programs funded by
the President's Emergency Plan for AIDS Relief and the Global
Fund.
One of the ethical issues raised at the Conference
concerned informed consent among vaccine trial participants in
developing countries. Generally, it is recommended that an
individual have a sixth grade education level for all informed
consent processes. This standard is inapplicable in much of
Africa, where most of the population is illiterate. In
addition, in countries where participants' beliefs about health
and illness differ from those of scientists, it is critical
that researchers be sensitive to local beliefs, values, and
practices. It is important that researchers use local language
and concepts in explaining vaccine trials and ensuring that
participants truly understand how trials work. Some cultures
are far less individualistic than Western cultures, and the
needs of the community outweigh often those of the individual.
In these situations, researchers are developing methods to
ensure that the decision to participate in a trial is made by
an individual and not by a community leader or representative.
Given the challenges of illiteracy and cultural differences,
experts are continuing to explore the best methods to ethically
obtain informed consent in developing countries.
The Importance of Including Women, Adolescents, and Children in
Clinical Trials
To date, AIDS vaccine trials have focused almost
exclusively on adults. However, given the alarmingly high HIV
prevalence rates in adolescents--especially females--in Sub-
Saharan Africa, some experts argue that the ideal AIDS vaccine
would target adolescents, prior to their sexual debut. \8\ In
addition, a vaccine for infants could help prevent the
transmission of HIV through breast milk, which is the primary
source of nourishment for most newborns in the developing
world. Many experts in the field agree that an AIDS vaccine
must ultimately include children, but that conducting the
necessary research raises a host of scientific and ethical
concerns. Because women and girls constitute the fastest
growing population in Sub-Saharan Africa to become infected
with HIV, it is imperative that the scientific community ensure
the inclusion of women in the pursuit of an AIDS vaccine.
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\8\ According to UNAIDS, in 2005 in Sub-Saharan Africa, among young
people aged 15-24 years, an estimated 4.6% of women and 1.7% of men
were living with HIV. See UNAIDS/WHO AIDS Epidemic Update, December
2005, p. 17.
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Enrolling children and adolescents in such trials, however,
is controversial because in many places, this would clash with
cultural beliefs against discussing sex with young people and
in acknowledging their sexual activity and risk of HIV
infection. In addition, government officials may be hesitant to
advocate for the involvement of children in trials as
communities may be suspicious and fearful of allowing their
children to serve as ``guinea pigs.'' The issue of ``informed
consent,'' already a challenge when dealing with adult
participants in clinical trials, would be event more
complicated when dealing with minors. The issue of including
children and minors in clinical trials will require further
debate by AIDS vaccine researchers, and the concerns of
representatives from developing countries must be considered.
Regulatory Issues
Finally, one of the issues raised by speakers at the
Conference was the issue of regulating AIDS vaccines.
Currently, there is no consensus as to what properties an AIDS
vaccine will need in order to be granted a license. Given the
variety of strains of HIV, it is also not clear whether
countries will require a vaccine that has been proven effective
in one or several regions to be tested again in local
populations or against certain strains. Moreover, each country
or region has its own licensing authority with its own
requirements. Therefore, it will be impossible for vaccine
producers to apply for a single license that is valid
everywhere.
Regulatory agencies in developing countries often lack the
capacity to review new products, such as an AIDS vaccine.
Authorities in these countries will likely look to developed
countries or the World Health Organization for guidance in
licensing a particular AIDS vaccine but, as has been the case
with the regulation of anti-retroviral drugs, each country will
ultimately need to reach its own conclusions. AIDS vaccine
researchers, activists, and policy makers need to begin to
consider how to streamline the regulatory process for an AIDS
vaccine so as to prevent the delay in distribution of a vaccine
once one is developed.
Concluding Thoughts and Recommendations
Given the rate at which the HIV/AIDS pandemic continues to
spread around the world, and with growing concerns about
``second wave'' countries like Russia, India, China, Nigeria,
and Ethiopia, it is critical that a way to prevent the spread
of this disease is found. The best hope for such prevention is
a vaccine. Although the biggest hurdles to the development of
an effective AIDS vaccine are scientific, more needs to be done
to accelerate the research behind this effort and to address
the non-scientific hurdles to developing such a vaccine. Donors
should collaborate so that AIDS treatment, counseling, and
testing programs support on-going vaccine trials. Activists and
policymakers need to work with the private sector to implement
meaningful incentives that will create viable markets and
encourage increased private sector activity in this area.
Although experts agree that an effective AIDS vaccine is
possible, it will take a greater commitment from a range of
governments, organizations, scientists and committed
individuals to create a vaccine to end the AIDS pandemic.