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" ! COMMITTEE PRINT 109TH CONGRESS

1st Session

S. PRT.

2006

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

Printed for the use of the Committee on Foreign Relations

Available via World Wide Web: http://www.access.gpo.gov/congress/senate

COMMITTEE ON FOREIGN RELATIONS

RICHARD G. LUGAR, Indiana, Chairman

CHUCK HAGEL, Nebraska

LINCOLN CHAFEE, Rhode Island

GEORGE ALLEN, Virginia

NORM COLEMAN, Minnesota

GEORGE V. VOINOVICH, Ohio

LAMAR ALEXANDER, Tennessee

JOHN E. SUNUNU, New Hampshire

LISA MURKOWSKI, Alaska

MEL MARTINEZ, Florida

JOSEPH R. BIDEN, Jr., Delaware

PAUL S. SARBANES, Maryland

CHRISTOPHER J. DODD, Connecticut

JOHN F. KERRY, Massachusetts

RUSSELL D. FEINGOLD, Wisconsin

BARBARA BOXER, California

BILL NELSON, Florida

BARACK OBAMA, Illinois

KENNETH A. MYERS, JR., Staff Director

ANTONY J. BLINKEN, Democratic Staff Director

(II)

CONTENTS

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

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)

(1)

1For 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.

2005 AIDS VACCINE INTERNATIONAL

CONFERENCE, MONTREAL, CANADA,

SEPTEMBER 6–9, 2005

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

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 vacVerDate 11-MAY-2000 13:26 Jan 06, 2006 Jkt 000000 PO 00000 Frm 00007 Fmt 6633 Sfmt 6633 25334.TXT SFRELA2 PsN: SFRELA2
2

2For 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.

cine 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

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

3

3When collecting data on immunogenicity, researchers are examining the strength and

breadth of the immune response of a trial vaccine. 4For more information on the Global HIV Vaccine Enterprise, see http://www.hivvaccineenterprise.org.

gather both safety and immunogenicity3 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.)

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.

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 compoVerDate 11-MAY-2000 13:26 Jan 06, 2006 Jkt 000000 PO 00000 Frm 00009 Fmt 6633 Sfmt 6633 25334.TXT SFRELA2 PsN: SFRELA2
4

5For more information on the CHAVI, see http://www.chavi.org. 6For 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. 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.

nent 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.

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

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

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

5

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.

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.

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

6

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 antiretroviral 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.

Æ