Investing in Vaccines

Children

and the Future

I V Iw w w. i v i . i n t

Copyright 2007-International Vaccine Institute All rights reservedInternational Vaccine Institute Kwanak P O Box 14 Seoul Korea 151 600Tel 82 2 872 2801 Fax 82 2 872 2803 Contact iviinfo@ivi.int for more information.www.ivi.int

4 Letter from the Director-General

5 Goal & Mission

The IVI & Millennium Development Goals

6 Historical Landmarks

7 Board of Trustees

8 Scientific Advisory Group

9 Signatory Countries

Recent Growth

10 The IVI’s Achievements

Organizational Structure

11 Programs of the IVI

11 Translational Research

13 Laboratory Sciences

15 Training and Technical Assistance

16 Future Directions of the IVI

17 Donors

Major donors

Korea Support Committee

18 International Collaborators

IVI scientist Dr. Jacqueline Deen with children atan IVI research site in Kolkata, India

CONTENTS

Dear Friends,We live in an extraordinarily exciting era in which the fruits of biotechnology offer the prospect of new vaccines against diseases for which no previous vaccines existed and of vastly improved versions of existing vaccines. While this revolution in vaccinology providesbreathtaking prospects for disease prevention, it is sobering to note that many vaccines that are routine public-health tools for theindustrialized world are not used in programs for the poor in the developing world, and that the discovery of vaccines against diseasesthat primarily afflict the developing world has been painfully slow due to a lack of economic incentives.

The International Vaccine Institute (IVI), located in Seoul, the Republic of Korea, was established to assist efforts to close the gap in vaccines for the developing world versus those for the industrialized world by conducting research and delivering technical assistance.The IVI is the world's only international research organization devoted solely to bringing new vaccines to the poor populations of thedeveloping world. To date, 40 countries and the WHO have signed the IVI Establishment Agreement.

The work and the growth of the IVI is part of a larger revolution in public sector commitment to closing the gap in vaccines for the rich and the poor. The GAVI Alliance has been extraordinarily successful in mobilizing new support for the purchase and deployment of neededvaccines in the public health programs of developing countries and has also launched support for research on new vaccines and vaccinetechnologies. In addition, various organizations such as the Bill & Melinda Gates Foundation, the U.S. National Institutes of Health, the EuropeanUnion, and the Wellcome Trust are committing greatly increased resources for vaccine research and development. There have also been majorpositive changes in the vaccine industry both in developed and developing countries. With respect to the latter, an ongoing story of great importis the astonishing evolution of many producers in developing countries.

During the years since the IVI was established in 1997, the Institute has become an important partner in global efforts to develop anddeploy new vaccines for the poor. It has conducted major programs of field research on new vaccines against diarrheal, respiratory, andflavivirus infections in 22 countries of Asia, Africa, and Latin America. Especially exciting in this regard was the recent launch of a collaborativeproject with the Academy of Medical Sciences of the Democratic People’s Republic of Korea (DPRK) on vaccines for DPRK children againstcentral nervous system infections. It has also provided technical assistance in vaccine production, regulation, and evaluation to professionals inmore than 20 countries in Asia, Africa, and Latin America.

The IVI's growth has been made possible by generous support from an increasing number of donors. The Republic of Korea has played a pivotal role in this respect, providing a portion of the IVI's operating budget, as well as a headquarters building with state-of-the-artlaboratories. The recent completion of this beautiful building, located on the campus of Seoul National University, has allowed the Institute tolaunch an exciting new laboratory sciences program. The Laboratory Science Division has already made significant scientific advances, includingthe development of novel adjuvants that have the potential to significantly increase the effectiveness of oral vaccines, the development of newanimal models for Shigella to evaluate future vaccines, and the development in collaboration with the U.S. National Institutes of Health of a Viconjugate typhoid vaccine with the potential for use in infants. The construction of a new Biosafety Level 3+ laboratory in our headquarters willalso allow the IVI to develop vaccines against dangerous pathogens, including avian influenza (H5N1).

In closing, I would like to acknowledge the importance to our programs of the collaboration of many institutions and individuals, from both the private and public sectors and from both the industrialized and developing worlds. And I would like to thank especially the scientists, public health officials, and other collaborators in developing countries who have allowed us to join with them in their work to reduce morbidity and mortality in their countries. It has been an honor to have shared the hopes and aspirations of these dedicated persons.

Sincerely,

John D. Clemens, M.D.

Goal & Mission

The IVI & Millennium Development Goals

GoalThe IVI is founded on the belief that health in developing countries can be dramatically improved by the development, introduction, anduse of new and improved vaccines and that these vaccines should be developed through a dynamic interaction among science, publichealth, and business. The IVI will be a center of science for the public interest, where this dynamic interaction can take place throughresearch, training, technical assistance, and information dissemination.

MissionThe IVI will contribute to the reduction of vaccine preventable diseases in developing countries by collaborative research thatgenerates the evidence needed for rational introduction of new vaccines, supported by programs of basic and applied laboratoryresearch, product development, training, and technical assistance.

At the United Nations Millennium Summit in September 2000 world leaders placed development at the heart of the global agenda byadopting the eight Millennium Development Goals (MDGs), which constitute an ambitious agenda to significantly improve the humancondition. The MDGs set clear targets for reducing poverty, hunger, disease, illiteracy, environmental degradation, and discriminationagainst women by 2015. The IVI is actively working to make a valuable contribution to achieving the following four MDGs:

MDG 1: “Eradicate extreme poverty and hunger”

By preventing unnecessary deaths and allowing people, especially children, to lead healthy lives, the IVI contributes to alleviatingpoverty and strengthening economies.

MDG 4: “Reduce child mortality” and

MDG 6: “Combat HIV/AIDS, malaria and other diseases”

The research programs at the IVI contribute to the target of reducing by two-thirds, between 1990 and 2015, the under-five mortalityrate by accelerating the introduction of new-generation vaccines against diarrhea and respiratory infections, and against Japaneseencephalitis and dengue fever. Together these diseases claim the lives of over four million persons each year, most of whom arechildren living in impoverished conditions in developing countries.

MDG 8: “Develop a global partnership for development”

The mission of the IVI is to develop and accelerate the introduction of new vaccines at affordable prices into the public healthprograms of developing countries. The IVI facilitates the transfer of vaccine technology to pharmaceutical companies in developingcountries to create cost-effective vaccines for the world's poor. The Institute also provides training and technical assistance for theclinical evaluation of vaccines and vaccine production and regulation to professionals in developing countries.

Letter from the Director-GeneralDr. John D. Clemens, Director-General of the IVI, is an international expert on vaccine evaluation indeveloping countries. Before joining the IVI in 1999, he held senior positions at the United StatesNational Institutes of Health. He has also served as a long-term advisor to the World Health Organization(WHO) and serves as a member of the GAVI Alliance Board.

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Board of Trustees

Prof. Ragnar Norrby - ChairmanDirector General, Swedish Institute forInfectious Disease Control, Stockholm, Sweden

Dr. Margaret Ann Liu - Vice-ChairProTherimmune,Visiting Professor, Karolinska Institute,Stockholm, Sweden

Prof. Barry R. Bloom - Chairman EmeritusDean, Harvard School of Public Health,Boston, MA, USA

Dr. Abdul Rahman al-AwadiExecutive Secretary, Regional Organizationfor Protection of Marine Environment(ROPME), Dahia Abdullah Salem, Kuwait

Dr. John D. ClemensDirector-General, International VaccineInstitute, Seoul, Republic of Korea

Prof. Gordon DouganPrincipal Research Scientist, WellcomeTrust Sanger Institute, Cambridge, U.K.

Dr. Roger GlassDirector, Fogarty International Center,National Institutes of Health, Bethesda,MD, USA

Dr. Michel GrecoFormer President, sanofi pasteur,Lyon, France

Dr. Julian Lob-LevytExecutive Secretary, The GAVI Alliance, Geneva, Switzerland

Prof. Nay Htun - Chair of IVI’s InstituteSupport CouncilProfessor, Stony Brook Southampton,State University of New York, NY, USA

Dr. I. Nyoman KandunDirector General, Disease Control &Environmental Health, Ministry of Health, Government of IndonesiaJakarta, Indonesia

Mr. Song Young-wan Director General, InternationalOrganizations Bureau, Ministry of ForeignAffairs & Trade, Seoul, Republic of Korea

Prof. Samuel KatzProfessor Emeritus, Department ofPediatrics, Duke University Medical Center,Durham, NC, USA

Prof. Kim Shin-bok Vice President, Seoul National University,Seoul, Republic of Korea

Dr. Marie-Paule Kieny Director, Initiative for Vaccine Research(WHO/IVR), World Health Organization Geneva, Switzerland

Dr. Nguyen Tran Hien Director, National Institute of Hygiene andEpidemiologyFaculty of Public Health, Hanoi MedicalUniversityHanoi, Vietnam

Dr. Shigeru OmiRegional Director, WHO Regional Office forWestern Pacific (WPRO), Manila, Philippines

Dr. Regina RabinovichDirector, Infectious Diseases, Global HealthProgram, Bill & Melinda Gates Foundation,Seattle, WA, USA

Dr. Francisco SonganeDirector, Partnership for Maternal, Newborn& Child Health (PMNCH), Geneva, Switzerland

Prof. B.A.M. van der ZeijstDirector, Netherlands Vaccine Institute,Al Bilthoven, The Netherlands

Dr. Ann-Mari Larsdotter SvennerholmProfessor, Department of Microbiology andImmunology, Goteborg University, Sweden

Dr. Isabel Noguer ZambranoDeputy Director, International ResearchPrograms and Institutional Relations,Instituto de Salud Carlos III, Ministry of Health and Consumption, Madrid, Spain

Dr. Akira HommaDirector, Institute of Technology forImmunologicals,Bio-Manguinhos of the Oswaldo Cruz,Foundation (Fiocruz),Rio de Janeiro, Brazil

Members of the IVI Board of Trustees and representatives of IVI’s collaborating institutions during the annual Board meeting held in Kolkata, India inMarch 2007.

Historical Landmarks

Oct 2007

May 2007

Jul 2006

Apr 2006

Oct 2005

Oct 2004

Sept 2004

Jul 2003

Jun 2003

Jun 2003

Mar 2002

Jan 2000

Apr 1999

Apr 1999

Oct 1997

May 1997

Dec1995

Jan 1995

Jun 1994

Mar1994

Sept 1993

Sept 1990

Commemoration of IVI’s 10th anniversary

Start of construction of BSL3+ laboratories. Launch of projects to introduce vaccines forchildren in the Democratic People’s Republic of Korea (DPRK).

Cholera Vaccine Initiative (CHOVI) launched with a US$22 million grant from the Bill &Melinda Gates Foundation.

IVI Board of Trustees elects Prof. Ragnar Norrby as its new Chairman.

Eighth Anniversary ceremony held in the presence of the ROK First Lady MadameKwon Yang-suk. IVI staff size exceeds 100, and budget tops US$15 million.

IVI headquarters building is inaugurated by President Roh Moo-hyun of the Republicof Korea.

Madame Kwon Yang-suk, First Lady of Korea, becomes the Honorary President of theKorea Support Committee for IVI.

The Pediatric Dengue Vaccine Initiative (PDVI) receives a US$55 million grantfrom the Bill & Melinda Gates Foundation

The IVI Board of Trustees elects Prof. Samuel Katz as its new Chairman. Former WHODirector-General, the late Lee Jong-wook visits IVI.

Opening of the new headquarters building, generously donated by the Governmentof Korea, and initiation of IVI's new Laboratory Sciences Division

The Board of Trustees meets with Mr. Kim Dae-jung, President of the Republic ofKorea, at the presidential office of Cheong Wa Dae.

Launch of the Diseases of the Most Impoverished (DOMI) Program, with a US$40million grant from the Bill & Melinda Gates Foundation.

Madame Lee Hee-ho, First Lady of Korea, becomes the Honorary President of theKorea Support Committee for the IVI.

The Board of Trustees appoints Dr. John Clemens as the first Director of IVI.

Inaugural meetings of the governing Board of Trustees and the Institute SupportCouncil convene in Seoul, with Prof. Barry Bloom as the Board's first Chairman.

IVI's Establishment Agreement goes into effect after receiving three ratificationsat United Nations Headquarters in New York.

The Government of the Republic of Korea (Ministry of Education and Human ResourcesDevelopment) sets up special task force at Seoul National University for theestablishment of the IVI (chaired by Prof. Park Sang-dai).

UNDP opens an interim office of the IVI on the campus of Seoul National Universityin Seoul, the Republic of Korea.

The Site Selection Committee, meeting at UNDP, recommends that the IVI belocated in Seoul, the Republic of Korea, and that the Institute carry out its activitiesthrough close partnerships with centers of excellence in other countries in theregion.

Six Asian countries submit proposals to UNDP to host the IVI.

Based on a feasibility study, a formal proposal to establish the IVI as an outgrowthof the CVI in a developing country in Asia is adopted by UNDP.

The World Summit on Children at the United Nations adopts a declaration calling forconcerted international action to promote children's health in developing countries,leading to the creation of the Children’s Vaccine Initiative (CVI).

(As of Sept. 2007)

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Signatory Countries

Recent Growth

Bangladesh Bhutan Brazil China Cote d’Ivoire Ecuador Egypt India Indonesia

Israel Jamaica Kazakhstan Kuwait Kyrgyzstan Lebanon Liberia Malta Mongolia

Myanmar Nepal Netherlands Oman Pakistan Panama Papua New Guinea Peru Philippines

Republic of Korea Romania Senegal Slovak Republic Spain Sri Lanka Sweden Tajikistan Thailand

Turkey United Arab Emirates Uzbekistan Vietnam World Health Organization

(40 countries and WHO, as of Sept. 2007)

The IVI has experienced rapid growth in its budget and staff since its establishment in 1997. Its staff now numbers 130 and comesfrom 20 countries in Asia, Africa, Europe, North America, and Australia. Its budget has also grown to over US$25 million per year.

Staff Growth since 1997

1997 1997

2

4

6

8

10

12

14

16 15.5

17.2

25.8

1012

18

30

40

50

70

93

105

121

130

1998 1998 1999 1999 2000

2000 2001 2001 2002

2002 2003 2003 2004

2004 200520052006

200620072007

Budget Growth since 1997 (US$ million)

Scientific Advisory Group

The IVI Scientific Advisory Group (SAG), established in 2000, is composed ofinternational experts in vaccine sciences and public health. The SAG meets yearly toreview the scientific programs of the Institute and to advise the Director-General.

The Scientific Advisory Group meeting in session at the IVI headquarters in Seoul, Republic of Korea, April 2006.

Prof. Robert Black - Chair

Professor, International Health, Johns Hopkins University School of Hygiene & Public Health, Baltimore, USA

Dr. Costante Ceccarini

Independent consultant, Italy

Prof. Ian David Gust

Emeritus Professor, University of Melbourne, Australia

Prof. Jan Holmgren

Professor, Department of MedicalMicrobiology and Immunology,Goteborg University, Sweden

Prof. Kim Sun-young

Professor, Institute of Molecular Biologyand Genetics, Seoul National University,Republic of Korea

Prof. Byoung S. Kwon

Professor and Director, ImmunomodulationResearch Center, University of Ulsan, Korea,and Professor, Louisiana State UniversityMedical Center, New Orleans, USA

Prof. Ira M. Longini, Jr.

Professor, Department of Biostatistics,University of Washington School of PublicHealth and Community MedicineSeattle, USA

Prof. Moon H. Nahm

Professor, Department of Pathology,University of Alabama at Birmingham,USA

Prof. Pearay L. Ogra

Professor, Department of Pediatrics, State University of New York at Buffalo,Women & Children's Hospital, USA

Prof. Peter Smith

Professor, Department of Epidemiologyand Population Health,London School of Hygiene & TropicalMedicine, UK

Prof. Yoshifumi Takeda

Professor, Department of Food and HealthSciences, Faculty of Human Life Sciences,Jissen Women’s University,Tokyo, Japan

Facilities Committee

Prof. Gordon Dougan

Member of the Board of Management,Wellcome Trust Sanger Institute,Wellcome Trust Genome Campus,Cambridge, UK

Dr. Margaret Ann Liu

ProTherimmune,Visiting Professor, Karolinska Institute,Stockholm, Sweden

(As of Sept. 2007)8 9

Translational Research

The Translational Research Programs of the IVI conduct the diverse types of research needed to provide the evidence required bypolicymakers to introduce new vaccines into public health programs for the poor in developing countries. These studies includeassessments of the disease burden and risk factors for specific diseases in different populations; clinical trials and demonstrationprojects of vaccines; economic analyses of the cost-effectiveness of introducing new vaccines; assessments of the publicdemand and willingness to pay for new vaccines; and policy assessments of the feasibility and financial sustainability of introducingnew vaccines. The multi-disciplinary group of scientists in this division includes experts in epidemiology, clinical trials, computerscience, biostatistics, economics, behavioral sciences, and policy analysis.

1. Diseases of the Most Impoverished (DOMI) Program

Donor support: Bill & Melinda Gates Foundation, Japan International Cooperation Agency (JICA), Ministry of Education andHuman Resources Development (MOE&HRD, Republic of Korea), GlaxoSmithKline Biologicals (GSK), Sartorius AG, WellcomeTrust, Government of Kuwait, Swedish International Development and Cooperation Agency (SIDA), AusAID, Rockefeller Foundation, UBSOptimus Foundation, National Institute for Biological Standards and Controls (UK), Medecins Sans Frontieres, Goteborg University, Emergent Europe, AVANT Immunotherapeutics, Swedish Bacterial Laboratories

Goal: To accelerate the rational introduction of new-generation vaccines against cholera, shigellosis, and typhoid fever into public healthprograms of selected developing countries in Asia and Africa through a program of research, technical assistance, and technology transfer for vaccine production.

Activities (countries participating):

- Epidemiologic studies of disease burden (Bangladesh, China, India, Indonesia, Mozambique, Pakistan, Thailand, Vietnam)- Clinical trials of experimental vaccines against cholera (Bangladesh, India, Vietnam)- Demonstration projects of existing new-generation vaccines against cholera and typhoid fever (China, India, Indonesia, Mozambique,

Pakistan,Vietnam)- Studies of the cost-of-illness of cholera, shigellosis and typhoid fever, and of the cost-effectiveness of vaccination (Bangladesh, China, India,

Indonesia, Mozambique, Pakistan, Thailand, Vietnam)- Socio-behavioral studies of perceptions of cholera, shigellosis, and typhoid fever and the need for vaccination (Bangladesh, China, India,

Indonesia, Mozambique, Pakistan, Thailand, Vietnam)- Policy research on vaccine introduction (Bangladesh, China, India, Indonesia, Pakistan, Thailand, Vietnam)- Vaccine production technology transfer (India, Indonesia, Pakistan, Vietnam)

2. Cholera Vaccine Initiative (CHOVI)

Donor support:Bill & Melinda Gates Foundation, Government of Kuwait, MOE&HRD (Republic of Korea), SIDA

Goal: To control cholera by developing and deploying safe and effective oral cholera vaccines in populations at risk for endemic or epidemiccholera, with the ultimate aim to enable these vaccines to be pre-qualified by WHO for use by endemic countries and UN agencies.

Activities:- Technical transfer of a reformulated oral killed whole-cell (WC) vaccine (2-dose) to high-quality vaccine producers in India

(Shantha Biotechnics) and Indonesia (BioFarma)- Clinical trials of the WC vaccine in India and Indonesia to enable licensure of the vaccine in both countries, including

completion of a large-scale Phase III trial in Kolkata, India- Phase II and III clinical trials of a one-dose oral live attenuated vaccine candidate (Peru-15) in Bangladesh and India

3. Pediatric Dengue Vaccine Initiative (PDVI)

Donor support: Bill & Melinda Gates Foundation, Korea International Cooperation Agency (KOICA), Rockefeller Foundation,Government of Kuwait, MOE&HRD (Republic of Korea), SIDA

Goal: To accelerate the development, evaluation, and introduction of vaccines against dengue fever into public health programs indeveloping countries.

The IVI’s Achievements

Since its establishment in 1997, the IVI has:

Established major research programs in 22 countries of Asia, Africa, and Latin America to:- Determine the disease burden of invasive bacterial infections of childhood, especially Haemophilus influenzae type b (Hib)- Assess the disease burden of rotavirus diarrhea in children- Accelerate the development and provide evidence for rational introduction of vaccines against cholera, shigellosis, and typhoid fever

(Diseases of the Most Impoverished Program)- Accelerate the development and introduction of new vaccines against dengue fever for public health programs for the poor in Asia and Latin

America (Pediatric Dengue Vaccine Initiative)- Provide evidence for rational introduction of vaccines against Japanese encephalitis into programs for children in Asia- Assess the efficacy of new vaccines against enterotoxigenic Escherichia coli- Develop model systems for assessing the safety of vaccines used in developing countries

Implemented a program of laboratory research at the IVI headquarters in Seoul dedicated to vaccine development, withactivities in molecular microbiology, clinical immunology, molecular vaccinology, mucosal immunology, and vaccine processdevelopment.

Developed or co-developed 3 vaccines against cholera and typhoid fever, and initiated technology transfer to developing countryproducers.

Provided training and technical assistance to professionals in Asia and Africa on:

- Clinical evaluation of vaccines- Vaccine production and regulatory issuesOrganized and conducted a heavily subscribed annual course on vaccinology for professionals in the Asia-Pacific region.

Established a group of affiliated laboratories in Korea and a network of collaborating laboratories in Europe and the United States.

Established a post-doctoral training program in the network of IVI's collaborating laboratories.

Programs of the IVI

Organizational Structure

1 0 1 1

Donor support: Bill & Melinda Gates Foundation; Korea Research Institute of Bioscience and Biotechnology; Ministry of Education & HumanResources Development (MOE&HRD, Republic of Korea); Japan Society for the Promotion of Science; Korea Science and EngineeringFoundation; Korea Research Foundation; Ministry of Science and Technology (Republic of Korea); Sartorius AG; Government of Kuwait; SwedishInternational Development and Cooperation Agency (SIDA), Merck & Co.

1. Molecular Microbiology Program

Goal: To identify microbial pathogens from field specimens to better understand the molecular epidemiology, pathogenicmechanisms, and genetic diversity of bacterial pathogens.

Activities: - Genotyping of bacteria (Shigella, Salmonella, M. tuberculosis, and Vibrios) and viruses (influenza, SARS)- Computational management of data (bioinformatics)

2. Clinical Immunology Program

Goal: To assess immune responses to vaccines in infants and children.

Activities:-Establishment of standardized immunoassays for assessing immune responses to human vaccines. The development of

quality-controlled immunoassays for V. cholerae and S. pneumoniae has been completed and is being extended to other pathogens (S. typhi, S. paratyphi, influenza).

- Development of miniaturized assays for testing blood samples and mucosal secretions from pediatric subjects

3. Molecular Vaccinology Program

Goal: To identify novel protective antigens to be incorporated in new vaccines.

Activities: - Design and production at laboratory scale of plasmid DNA-based vaccines and live-attenuated recombinant bacteria and viruses for mucosal

and systemic immunization- Identification of protective antigens to be incorporated into candidate vaccines (e.g. Shigella and influenza, including H5N1)

Laboratory Sciences

After the completion of its new headquarters building in 2003, the IVI established laboratory programs dedicated to vaccineresearch. The programs involve more than 30 persons supervised by eight senior scientists trained in areas spanning from molecularbiology to microbiology, bioinformatics, mucosal immunology, clinical immunology, and vaccine production. Equipped with state-of-the-art instruments, the IVI's laboratories will soon benefit from the addition of a combined (animal/clinical) high security (BSL3+)laboratory for conducting studies on dangerous pathogens. These programs provide quality-controlled assays and procedures fortyping microbes from field isolates and conducting technology transfer activities to affiliated laboratories in developing countries. Extensiveefforts are being devoted to designing novel cost-effective vaccine formulations amenable to large-scale production, as well as novel adjuvant molecules for enhancing vaccine potency.

Activities (countries participating):

- Strategic Partnerships (Belgium, Brazil, France, India, Switzerland, USA)Participation in or formation of partnerships with organizations developing and evaluating dengue vaccines and diagnostics, andorganizations involved in introducing vaccines into national immunization programs.

- Supportive Research and Development (France, Myanmar, Thailand, UK, USA)Support development of standard diagnostic tests and assays to improve diagnosis of acute dengue virus infection, to further thedevelopment of assays to assess post-infection and post-vaccination immunity, and to identify those at risk for antibody-enhanceddisease.

- Vaccine Evaluation (Nicaragua, Vietnam, Thailand, Colombia, India)Sponsoring of activities that will support the evaluation of dengue vaccines in large-scale clinical trials and post-licensureeffectiveness trials. Creation of a consortium of field sites to host the trials, and work with partners to design evidence-basedprotocols for implementation of vaccination programs and to measure outcomes.

- Vaccine Access (Brazil, Cambodia, El Salvador, Guatemala, Malaysia, Panama, Thailand, Venezuela)Conduct activities to estimate the burden of disease, assess the impact on disease and cost-effectiveness of various denguevaccination strategies, strengthen dengue surveillance, develop and promote plans for national and international procurementand distribution of the vaccine for the poor in dengue endemic countries, and develop effective communications about dengue asa vaccine-preventable disease.

4. Japanese Encephalitis (JE) Vaccine Program

Donor support: Korea International Cooperation Agency (KOICA, Republic of Korea), MOE&HRD (Republic of Korea), Ministry of Unification(MOU, Republic of Korea), Children's Vaccine Program at PATH, Government of Kuwait, SIDAGoal: To provide the evidence necessary for the rational introduction and use of vaccines against Japanese encephalitis inpublic health programs for poor populations living in developing countries of Asia.Activities (countries participating):- Epidemiologic studies of the disease burden (India, Indonesia, Vietnam)- Clinical studies of long-term neurobehavioral sequelae of JE (China)- A model program of JE immunization (Vietnam)- Evaluation of field effectiveness of locally produced JE vaccine (Vietnam)- Evaluation of the feasibility of JE vaccine introduction (DPR Korea)- Studies of the economic cost of JE illness and of the cost-effectiveness of vaccinating against JE (China, Indonesia, Vietnam)- Policy research on vaccine introduction (China, Vietnam)

5. Respiratory Pathogen Vaccines Program

Donor support: PneumoADIP Program at Johns Hopkins University, sanofi pasteur, GlaxoSmithKline Biologicals, Wyeth Pharmaceuticals,MOE&HRD (Republic of Korea), MOU, (Republic of Korea), Government of Kuwait, SIDA Goal: To provide an improved evidence base of disease burden statistics to assist the rational introduction of new-generation vaccinesagainst influenza, Haemophilus influenzae type b (Hib), Streptococcus pneumoniae, and Neiseria meningitidis into public health programsfor children and adults in Asia.Activities (countries participating):- Studies of the disease burden of invasive bacterial disease (Vietnam)- Studies of the disease burden of pneumococcal empyema (Australia, China, Indonesia, Republic of Korea Korea, Thailand, Vietnam)- Studies of the disease burden of influenza and impact of influenza vaccine in adults (China, Republic of Korea)- Studies of the feasibility of introducing Haemophilus influenzae type b (Hib) vaccine for children (DPR Korea, Vietnam)

6. Rotavirus Diarrhea Vaccine Program

Donor support: Rotavirus Vaccine Program at PATH, MOE&HRD (Republic of Korea), Government of Kuwait, SIDA

Goal: To provide the evidence needed for the introduction of new vaccines against childhood rotavirus diarrhea into routine infantimmunization programs.Activities (countries participating):- Studies of the disease burden and health care costs of rotavirus diarrhea in children (Cambodia, Lao PDR, Mongolia, Sri Lanka, Vietnam)- Studies of the safety and efficacy of new-generation, live attenuated, oral rotavirus vaccines (Vietnam)

7. Program on New Systems for Assessing Vaccine Safety in Developing Countries

Donor support: Government of Japan, MOE&HRD (Republic of Korea), UNDP, Government of Kuwait, SIDA

Goal: To develop innovative approaches for monitoring vaccine safety and evaluating hypotheses about alleged vaccine side effects indeveloping countries.Activities (countries participating):- Development of a dynamic large-linked database for studying rare but serious side effects of vaccines (Vietnam)

8. Tuberculosis Vaccine Program

BCG evaluation in Republic of Korea

Donor support: Korean Institute of Tuberculosis, Yonsei University, MOE&HRD (Republic of Korea), Government of Kuwait, SIDAGoal: To evaluate current BCG vaccination practices in the Republic of Korea in order to improve the BCG vaccination program for children.Activities (countries participating):Epidemiological and immunological studies on BCG vaccines in children in the Republic of Korea:- To determine BCG vaccination coverage by investigating BCG scars of children aged 1-9 years old- To analyze PPD tuberculin test responses and in vitro immune responses to M. tuberculosis and M. bovis BCG antigens among children

vaccinated with BCG.

1 2 1 3

Training and Technical Assistance

Donor support: Government of Republic of Korea, AusAID, Bill & Melinda Gates Foundation, GlaxoSmithKline Biologicals, Rockefeller Foundation,Sartorius AG, Government of Kuwait, Swedish International Development and Cooperation Agency (SIDA), Merck Vaccines

Goal: To provide training on modern methods and standards for vaccine production and evaluation, as well as on research methods needed togenerate evidence to inform vaccine policy. The division provides technical assistance to producers in developing countries for the production ofnew vaccines and participates as a trainer in the Global Training Network of the World Health Organization.

Activities (countries participating):- Annual International Advanced Course on Vaccinology- Training on Good Manufacturing Practices (GMP) in vaccine production (China, Vietnam)- Training on production and lot release testing of killed, oral cholera and Vi polysaccharide vaccines (China, Vietnam, India,Indonesia, Pakistan)- Training on Good Clinical Practice (GCP) standards and methods for trials of vaccines in humans (Bangladesh, Cambodia, China, India, Indonesia,

Pakistan, Philippines, Thailand, Vietnam)- Post-doctoral training in vaccine sciences (France, Republic of Korea, Sweden, United States, Japan, Vietnam, Mongolia)- Workshops on data management methods, microbiological techniques, and social science methods for field studies of vaccines (Bangladesh,

China, India, Indonesia, Mozambique, Pakistan, Thailand, Vietnam)- The Scholars in Residence Program, in which world-renowned scientists are invited to the IVI on a regular basis to give lectures and to share

their expertise with IVI scientists and the Korean scientific community- Clinical trials training course for Developing Country Vaccine Manufacturers Network (DCVMN) (Brazil, China, India, Indonesia, Republic of

Korea, South Africa, Vietnam)

Participants in the 7th International Advanced Course on Vaccinology in the Asia-Pacific Region, held at the IVI headquarters in Seoul, Republic ofKorea in May 2007.

4. Mucosal Immunology Program

Goal: To better understand the fundamental aspects of the mucosal immune response and to use this information to developeffective vaccines that can be administered without needles.

Activities:- Functional characterization of mucosal M cells and dendritic cells as cellular elements controlling uptake of vaccines and

induction of immunity at mucosal surfaces. This knowledge is being used to develop mucosal vaccines and to establish testsfor measuring mucosal immune responses.

- Development of formulations for improved delivery of vaccines. Animal models of influenza virus infection and shigellosisare being established to carry out pre-clinical efficacy testing of candidate vaccines against these pathogens. These studiescould lead to the development of dose-sparing vaccine strategies amenable to mass immunization against several entericand respiratory pathogens.

5. Vaccine Process Development and Technology Transfer Program

Goal: To develop, improve, and transfer to local producers the manufacturing and quality control technologies needed for vaccines againstdiseases of developing countries.

Activities: - Development of a quality controlled process technology for producing an oral vaccine against cholera- Production of a Vi capsular polysaccharide and Vi protein conjugate vaccines against typhoid fever, as well as quality control and

lot release assays for these vaccines- Production and purification of a ribosome-based vaccine against shigellosis. Laboratory scale lots have been produced and

consistency demonstrated. Pre-clinical testing in animals is ongoing.

The training and technical assistance program of the IVI consists of formal didactic as well as informal, hands-on training designed to increasethe capacity of developing country professionals in the vaccine sciences.

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Arizona State University, USAAusAIDBill & Melinda Gates FoundationKorean Government & organizations- Ministry of Education and Human Resources Development- Ministry of Science and Technology- Ministry of Unification- Korea Exchange Bank (KEB) Foundation- Korea Health Industry Development Institute- Korea Institute of Tuberculosis- Korea International Cooperation Agency (KOICA)- Korea Research Foundation- Korea Research Institute of Biology and Biotechnology- Korea Rural Development Administration- Korea Science and Engineering Foundation (KOSEF)- Seoul National UniversityGovernment of KuwaitThe GAVI AllianceJohns Hopkins University (PneumoADIP)Japan International Cooperation Agency (JICA)Rockefeller FoundationPATH (Program for Appropriate Technology in Health)

Portland State University, USASwedish International Development Cooperation Agency (SIDA)VIDO, University of Saskatchewan, CanadaUBS Optimus FoundationNagasaki University , JapanUnited Nations (UNDESA)United Nations Development Program (UNDP)U.S. National Institutes of Health (USNIH)U.S. Agency for International Development (USAID)U.S. National Science Foundation (NSF)World Health Organization (WHO)Wellcome Trust

Major Donors

Government & non-profit organizations:

Industry & individuals (over KRW10 million in cash) as of Sept. 2007

Contron Co., STC, Green Cross, Nonghyup (SNU Branch), Ace MembershipTransaction Co., Amway Korea, Daewon Housing Co. Ltd., DongmoonConstruction, Dongyang Construction, eB Co. Ltd., Emergent Europe, Genesis,GlaxoSmithKline, Goldwin Korea, GS Caltex, Hanbak CNT, Hwasankikong,Hyundai Engineering & Construction, Hyundai Heavy Industries, Kihung TourCo. Ltd., Korea Public Co. Ltd., KTB Assets Management, KTRD, KTS&C,Kumho Asiana, Lee Kyung Min Foret, LIG, Maiim, Merck & Co., Mr.KkangCompany, New Kyunggi Tour Co. Ltd., Orange Engineering, Chung Pal-do,Samyang Corp., Lee Sang-bum, sanofi pasteur, Sartorius AG, SBL Vaccines, SCFirst Bank, Shinpyung C&D, Sigong Tech, SK, Sky72 Golf Club, Smile FutureDental Clinic, S-Oil, Cho Wan-kyoo, Wyeth Pharmaceuticals, Young Joe E&C

Core funding to the IVI is provided by the governments of the Republic of Korea, Kuwait and Sweden. In addition, public- and private-sectordonors provide support for the Institute's research and programs.

A large number of prominent Korean citizens have joined together to form the Korea Support Committee (KSC) for the IVI. The Committeeis a vehicle for mobilizing resources within Korea and is under the leadership of Korea’s First Lady, Madame Kwon Yang-suk.

Madame Kwon Yang-suk, First Lady of the Republic of Korea,greets IVI Director-General Dr. John Clemens, at thepresidential office.

Madame Lee Hee-ho, former First Lady of the Republic ofKorea who served as Honorary President of the KSC for IVI,poses with IVI Board members, KSC members and IVI staff atthe presidential office in August 1999.

Korea Support Committee (KSC)

Future Directions of the IVI

1. Translational Research:

Expand program priorities to include additional diseases of importance, such as tuberculosis and emerging respiratory viruses, including avian influenza

Extend field research into additional countries of Asia and Africa

Initiate a vaccine evaluation unit in the Clinical Trials Center of Seoul National University

2. Laboratory Sciences & Vaccine Development:

Expand the laboratory programs in clinical immunology, mucosal immunology, molecular microbiology, molecular vaccinology, vaccineprocess development and technology transfer

Create a molecular microbiology platform to characterize pathogens, including emerging viruses, and select candidate vaccine antigens fromrepresentative strains

Establish improved tests for monitoring immunological responses to vaccines in children under field conditions

Develop new or improved vaccines against Shigella, cholera, and typhoid fever

Establish an influenza virus laboratory dedicated to the typing of avian and human influenza viruses, and develop molecular tools for improved surveillance of influenza infections in Asia

Evaluate the safety and immunogenicity of novel, non-invasive, vaccine formulations in humans

Facilitate technology transfer for production and quality control of new vaccines to qualified producers

3. Training & Information Dissemination:

Participate in training in vaccine production and regulation as part of the WHO Global Training Network

Organize periodic courses on the clinical evaluation of vaccines, Good Clinical Practice for vaccine trials, computerized approaches to datamanagement, and the design and conduct of economic, socio-behavioral, and policy analyses related to vaccine-preventable diseases andvaccine introduction

Conduct national and international symposia and workshops on scientific topics of relevance to vaccines for developing countries

Donors

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Nicaragua: National Center for Diagnosis and Reference, Ministry of Health

Pakistan: Aga Khan University; Amson Pharmaceuticals; Ministry of Health

Panama: Instituto Conmemorativo Gorgas

Philippines: Cebu Institute of Medicine; Research Institute for Tropical Medicine

Singapore: K.K. Women’s and Children’s Hospital

Sri Lanka: Epidemiology Unit, Ministry of Health; Lady Ridgeway Hospital

Sweden: Swedish Bacteriology Laboratories; Swedish Institute for Infectious Disease Control; Goteborg University

Switzerland: Berna Biotech; Medecins sans Frontieres

Thailand: Armed Forces Research Institute of Medical Science; Center for Disease Control (AFRIMS), Ministry of Public Health; Center forVaccine Development (CVD), Mahidol University; Faculty of Public Health, Mahidol University; Faculty of Tropical Medicine, MahidolUniversity

United Kingdom: Wellcome Trust Sanger Institute; Health Protection Agency; Imperial College of Science, Technology and Medicine;London School of Hygiene and Tropical Medicine; Emergent Europe; National Institute of Biological Standards and Control; University of Oxford

United States: Arizona State University; California Institute of Technology; Center for Biologics Evaluation and Research, Food and DrugAdministration; Centers for Disease Control and Prevention; Chiron Corp.; Colorado State University; Harvard University; Hawaii Biotech; HenryM. Jackson Foundation for the Advancement of Military Medicine; InViragen; Johns Hopkins Bloomberg School of Public Health; Johns HopkinsUniversity; Merck & Co.; National Institutes of Health; Naval Medical Research Institute; Portland State University; Program for AppropriateTechnology in Health (PATH); Purdue University; Schneider Institutes for Health Policy, Heller School, Brandeis University; The ScrippsResearch Institute; University of Alabama; University of California at Berkeley; University of California at Los Angeles; University of Maryland;University of North Carolina at Chapel Hill; University of Pennsylvania; University of Rochester Medical Center; University of Texas MedicalBranch at Galveston; Walter Reed Army Institute of Research; Washington University School of Medicine; Wayne State University; WestVirginia University; Wyeth Pharmaceuticals

Venezuela: Epidemiological Surveillance Headquarters, Ministry of Health and Social Development

Vietnam: Bach Mai Hospital; Hanoi Health Service; Ha Tay Provincial Preventive Medicine Center; Ho Chi Minh City Pasteur Institute;Hue City Hospital; Hue Provincial Preventive Medicine Center; Institute for Vaccines and other Biological Substances (IVAC); Khan HoaProvincial Hospital; Ministry of Health; National Institute of Hygiene and Epidemiology (NIHE); National Institute of Pediatrics; Nha TrangPasteur Institute; Ninh Hoa District Hospital; Phu Tho Provincial Center for Preventive Medicine; Phu Tho Provincial Hospital;VaBiotech; Wellcome Tropical Diseases Research Unit

International: World Health Organization

Australia: Queensland Institute of Medical Research

Bangladesh: ICDDR,B; Center for Health and Population Research; Dhaka Shishu Hospital, Dhaka

Belgium: GlaxoSmithKline Biologicals

Brazil: National Dengue Control Program Branch, Health Surveillance Secretariat, Ministry of Health; Federal University of Goias;Institute Oswaldo Cruz

Cambodia: Communicable Disease Control, Ministry of Health; Kantha Bopha Pediatric Hospital; National Dengue Control Program;National Center for Parasitology; Entomology and Malaria Control, Ministry of Health; National Immunization Program, Ministry ofHealth; National Pediatric Hospital; Epidemiology Unit, Institut Pasteur

Canada: Ministry of Health; University of Western Ontario; National Microbiology Laboratory, Public Health Agency of Canada

China: Anhui Provincial Anti-Epidemic Center; Beijing Friendship Hospital; Changchun Children’s Hospital; Chinese Centers forDisease Control; Dong-nan University School of Public Health; Fudan University; Guangxi Center for Disease Control and Prevention;Guangxi Maternal and Child Hosptial; Guangxi Medical University; Guangxi Centers for Disease Control and Prevention; GuangxiProvincial Hospital; Hebei Provincial Anti-Epidemic Center; Jiangsu Provincial Anti-Epidemic Center; Kunming Children’s Hospital;Lanzhou Institute of Biological Products; Lulong County Health and Anti-Epidemic Center; Ma-An-Shan Hospital; Ministry of Health;Nanning Second City Hospital; Sinovac Biotech; Suzhou Medical School; Wuhan Institute of Biological Products; Wuming County Hospital;Yongning County Hospital; Xiamen University; Hechi City Centers for Disease Control and Prevention; Jin Cheng Jiang Centers forDisease Control and Prevention

Cuba: Instituto of Tropical Medicine "Pedro Kouri"

Egypt: Ministry of Health and Population; U.S. Naval Medical Research Unit 3; Vacsera

El Salvador: Unit of Epidemiology, Ministry of Public Health and Social Assistance

Finland: National Public Health Institute

France: sanofi pasteur; Centre National de la Recherche Scientifique; Epicentre; Institut Pasteur

Germany: Sartorius AG; Max Planck Institute for Infection Biology (MPIIB), Max Planck Society for the Advancement of Science (MPG)

Guatemala: National Health Laboratory, Ministry of Public Health and Social Assistance

India: All India Institute of Medical Sciences (AIIMS); Bharat Biotech; Indian Council of Medical Research; International Center for GeneticEngineering and Biotechnology; INCLEN India; Ministry of Health; National Institute of Cholera and Enteric Diseases; Shantha Biotechnics;Indian Immunologicals Limited

Indonesia: BioFarma; Centers for Environmental Health and Disease Control; Central Public Health Laboratory; National Institute ofHealth Research and Development; Udayana University; U.S. Naval Medical Research Unit 2; Sanglah Hospital, Bali; Provincial Centersfor Disease Control, Bali; Ministry of Health

Japan: Life Sciences Division, Pentax; National Institute of Infectious Diseases; Research Institute for Microbial Diseases, OsakaUniversity; Institute of Medical Science, University of Tokyo; Nagasaki University

Korea: Busan National University Hospital; Catholic University Hospitals (St. Paul Hospital, Seoul, and St. Mary’s Hospital); ChangwonFatima Hospital; Chonbuk National University; Chonbuk Provincial Department of Health; Chonju Presbyterian Hospital; Green CrossClinical Reference Laboratory; Hallym University Hospital; Hanyang University Hospital; Inha University Hospital; Jeju NationalUniversity Hospital; Jung-Eub Hospital; Korea Research Institute of Bioscience and Biotechnology; Korea University; Korean Food andDrug Administration; Korean Institute of Tuberculosis; Korean National Institute of Health; Kyunghee University Hospital; LG LifeScience; Nam Won Medical Center; Pohang University of Science and Technology; Sam Kwang Clinical Laboratories; Seoul ClinicalLaboratories; Seoul National University; Social Security Research Institute; Soonchunhyang University Hospital; Standard Diagnostics;Ulsan University; Yonsei University; Won Kwang University Hospital

Laos: Mahosot Hospital; National Institute of Public Health, Ministry of Health

Malaysia: Faculty of Medicine, University of Malaya

Mongolia: Maternal and Child Health Research Center; Sukhbaatar District Hospital; Ministry of Health; Health Sciences University ofMongolia

Myanmar: Department of Medical Research (Lower Myanmar), Ministry of Health; Government of the Union of Myanmar

Mozambique: Ministry of Health, CHAEMS

International Collaborators

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