Building Capacity - International Vaccine Institute
Transcription
Building Capacity - International Vaccine Institute
2014 ANNUAL REPORT INTERNATIONAL VACCINE INSTITUTE Vaccine Discovery Development Delivery Capacity-Building Improving Health Saving Lives www.ivi.int VISION Developing countries free of suffering from infectious diseases MISSION Discover, develop and deliver safe, effective and affordable vaccines for developing nations ANNUAL REPORT 2014 TABLE OF CONTENTS 04 Letter from the Director General 07 IVI in Brief 08 Our Focus: Diseases of the Most Impoverished 09 Our Approach 10 Where We Work 13 2014 Milestones 15 Our Progress in 2014 22 In the Pipeline: Research Highlights 26 Building Success 27 Building Capacity 29 Board of Trustees 30 Scientific Advisory Group 31 Major Donors in 2014 32 Korea Support Committee for the IVI (KSC) 34 Major Partners in 2014 38 2014 Scientific Publications 42 2014 Financial Summary 43 IVI State Parties and/or Signatorie Letter from the Director General Dear Friends, I am pleased to introduce IVI’s 2014 Annual Report. This report presents the progress made by IVI despite the organizational transition that the Institute went through in 2014. Even though I joined IVI recently, I would like to acknowledge the contributions of the IVI team that I am proud to lead since March 2015. IVI experienced several successes and challenges in 2014, earmarked by a change in leadership. My predecessor Dr. Christian Loucq left IVI in early 2014 after approximately two years of leading the Institute and spearheading several strategic and operational initiatives to strengthen the organization. Besides Dr. Loucq, there were departures of other leadership team members. IVI also continued to face financial challenges but despite these issues, critical vaccine research and administrative support programs continued under the able leadership of John Morahan, who served as Chief Financial Officer and Acting Director General during that time. We continue to make progress in the discovery, development, and delivery of safe, effective and affordable vaccines, notably against cholera, typhoid, and dengue. We advanced the development of Korea’s first oral cholera vaccine through the establishment of a global access agreement with EuBiologics, a Korean vaccine manufacturer that IVI has been partnering with since 2010. EuBiologics agreed to produce the vaccine for the public-sector and to sell it an affordable price. With IVI’s support, EuBiologics received financing from the Global Health Investment Fund (GHIF) and Korean investors for the development and production of their cholera vaccine, EuvicholⓇ. EuvicholⓇ is expected to be WHO-prequalified in 2016, making it Korea’s first cholera vaccine for global health. We formed a new partnership with Incepta to develop and produce cholera and typhoid vaccines for Bangladesh. The partnership was initiated with technology transfers for the oral cholera vaccine and the typhoid conjugate vaccine from IVI to Incepta in 2014. As cholera and typhoid are major public health problems in Bangladesh, a local manufacturer committed to cholera and typhoid vaccines will help the fight against these diseases. In addition, we launched a large trial in Dhaka, Bangladesh for the oral cholera vaccine (Shanchol™). The vaccine (developed through IVI) is currently given as a two-dose regimen. However in recognition of the fact that a single-dose regimen would be easier to administer for outbreaks, a single-dose study was launched at the beginning of 2014 in collaboration with icddr,b. If we find that one dose of the vaccine is sufficient to protect against cholera, this could be a game-changer in how the vaccine will be used. We received a boost in the development of a new typhoid conjugate vaccine. IVI has partnered with SK Chemicals (Korea) and BioFarma (Indonesia) on the development of this vaccine. In late 2014, IVI received grant funding from the Bill & Melinda Gates Foundation to support further clinical vaccine development with these partners. 04 ANNUAL REPORT 2014 Preparations are being made for the clinical trials which are set for 2016. We wound down the Typhoid Surveillance in Africa Program (TSAP), which has been running since 2011. IVI coordinated standardized typhoid surveillance among field sites in 10 sub-Saharan African countries to generate data on the burden of typhoid in Africa. Findings from the multi-year surveillance are currently being analyzed for publication slated for 2015. We are moving on to the next research phase, which will assess severe typhoid and its outcomes in Africa. On the dengue front, as the lead agency for the Dengue Vaccine Initiative (DVI), IVI continued to coordinate the consortium (World Health Organization, Sabin Vaccine Institute and Johns Hopkins University), and conduct disease burden studies in Thailand, Vietnam and Colombia. In 2014, we expanded our research to new countries in Africa for the first time. New studies were initiated in Burkina Faso, and preparations were also made for the launch of field sites in Gabon, Kenya and Cambodia. Our International Advanced Course on Vaccinology in the Asia-Pacific Region marked its fourteenth year. The course, which takes place at IVI’s headquarters, aims to provide vaccine professionals from developing countries a comprehensive overview of vaccinology. Seventy-one trainees from 20 countries including Sudan, Yemen, Ethiopia, Ghana, Nepal, China, and Spain participated in the course. At the time of this report, IVI is in the process of renewal. Besides my arrival in early 2015, Dr. Laura Digilio joined in January, 2015 as Director of Development & Delivery, John Morahan officially became our Chief Operating Officer, and Dr. In-Kyu Yoon will be joining us as Director of the Dengue Vaccine Initiative (DVI) in August, 2015. The new leadership team has been working hard to prepare IVI for the challenges ahead and for ensuring that IVI will continue to make leading contributions to global health and vaccine research. The commitment of the leadership team and dedication of the IVI staff give me hope as we redefine and reposition IVI through this time. I would like to thank IVI’s donors and supporters who make our work possible: the Governments of the Republic of Korea and Sweden, the Bill & Melinda Gates Foundation, Germany’s Federal Ministry of Research and Education (BMBF), the Korea Support Committee for IVI (KSC), LG Electronics, Kia Motors, and the many small and large organizations and individuals in our host country of Korea. I would also like to thank IVI’s Board of Trustees for their guidance and time. Sincerely, Jerome Kim, M.D. Director General INTERNATIONAL VACCINE INSTITUTE 05 Vaccines Save Lives 6 ANNUAL REPORT 2014 IVI in Brief In 2011, the World Health Organization (WHO) estimated a total of 6.9 million children below the age of five died. Among the deaths, fifty-eight percent were from infectious diseases, and the majority was in Africa and South Asia. Many of these deaths can be prevented by vaccination. Vaccines are one of the most cost-effective tools in public health and have contributed greatly to the prevention and control of infectious diseases in the twentyfirst century. Thanks to vaccines, smallpox was eradicated and efforts are being made to eliminate polio and measles. While children in developed countries have benefitted from vaccination, many children in developing countries remain unprotected from potentially fatal, yet vaccine-preventable diseases. The International Vaccine Institute (IVI) was established in 1997 as an initiative by the United Nations Development Programme (UNDP) under the recognition that there was a need for an independent, not-for-profit international organization with the mandate to improve the health of children in developing nations through vaccines and vaccination. IVI’s mission is to discover, develop and deliver safe, effective and affordable vaccines for developing nations. Headquartered in Seoul, South Korea, IVI’s host country, IVI has thirty-five countries and the WHO as signatories. INTERNATIONAL VACCINE INSTITUTE 07 Our Focus: Diseases of the Most Impoverished Many vaccines against diseases primarily affecting low-income countries are not available for use, and many vaccines are not developed with the specific needs of those countries in mind. Factors contributing to these limitations are complex. In general, there is not enough information about disease burden and the impact of vaccination in developing countries. Vaccine manufacturers are often reluctant to undertake costly clinical development programs for vaccines that will be mostly used in developing countries with limited market potential. IVI aims to bridge the gap and make vaccines available and accessible for low-income countries. We focus on vaccines against: • Enteric and diarrheal diseases (cholera, enteric fever, Shigella) • Dengue 08 ANNUAL REPORT 2014 Our Approach Discover IVI is involved in all aspects of bringing a vaccine to reality: Discover new technologies to make new vaccines or improve existing ones. Develop Deliver Develop promising vaccine candidates for licensure and WHO prequalification by transferring the technology to manufacturers and partnering with them on clinical development. Deliver licensed vaccines in low-income countries by generating scientific data on the need for vaccines and the impact of vaccination for decision makers. Building capacity Building partnerships Building capacity in vaccinology in developing countries through technical assistance and training to promote self-sufficiency and sustainability in vaccines and vaccination. Building partnerships in Asia and globally for vaccines and global health. INTERNATIONAL VACCINE INSTITUTE 09 Where We Work Senegal Sudan Burkina Faso Ethiopia Colombia Gabon Kenya Brazil GuineaBissau Uganda Ghana Tanzania Malawi Madagascar South Africa Facts Headquartered at Seoul National University (ranked #1 in Korea and among the top 50 universities in the world) One of only 2 non-profit organizations to bring a vaccine to WHO prequalification (the oral cholera vaccine, Shanchol™, was prequalified in 2011) Driver for vaccine technology transfer in Asia with 6 tech transfer partners from 5 countries(Shantha Biotechnics, EuBiologics, BioFarma, VaBiotech, SK Chemicals, Incepta) 10 ANNUAL REPORT 2014 124 Number of staff North Korea Kyrgyzstan Bangladesh India Kazakhstan Mongolia Cambodia South Korea Pakistan Nepal Thailand 13 Number of countries represented by IVI staff Vietnam 27 Number of countries where IVI works (check world map) 100 Number of research collaborators 9 Number of vaccine products in pipeline INTERNATIONAL VACCINE INSTITUTE 11 Healthy Lives, Brighter Futures 12 ANNUAL REPORT 2014 2014 Milestones • Appointment of Dr. Jerome Kim as IVI’s Director General in late 2014. Dr. Kim is IVI’s third Director General. A medical do c tor by training and a colonel in the United States Army Medical Corps, Dr. Kim is a recognized leader in HIV res earch and vaccine development. Dr. Kim was the Principal Deputy and Chief of the Laboratory of Molecular Virology and Pathogenesis at the U.S. Military HIV Research Program (MHRP) and the U.S. Army's Project Manager for the HIV Vaccines and Advanced Concepts Evaluation and Staging. He was the U.S. Army lead for the Phase III HIV vaccine trial (RV144), the first to show that an HIV vaccine could protect against infection. Dr. Kim officially started his term in March 2015. • Advancements for Korea’s first cholera vaccine. Since 2010, IVI has been partnering with EuBiologics, a Korean biotechnology firm, on the development and production of an oral cholera vaccine. Significant progress was made in 2014 with the establishment of a global access agreement between IVI and EuBiologics in which EuBiologics agreed to produce the vaccine for the public-sector and to sell it an affordable price. With IVI’s support, EuBiologics received financing totaling $7.5 million from the Global Health Investment Fund (GHIF) and Korean investors for the oral cholera vaccine. Their vaccine, EuvicholⓇ, is expected to be WHO-prequalified in 2016, making it Korea’s first cholera vaccine for global health. • Expansion of support for typhoid conjugate vaccine development. IVI has been partnering with SK Chemicals (Korea) and BioFarma (Indonesia) on the development of a new typhoid conjugate vaccine. In late 2014, IVI received grant funding from the Bill & Melinda Gates Foundation to support further clinical vaccine development with these partners. Preparations are being made for the clinical trials which are set for 2016. • Launch of a large trial in Bangladesh for the oral cholera vaccine. The oral cholera vaccine (Shanchol™) developed through IVI comes in a two-dose regimen. However, as a single-dose regimen would be easier to administer for outbreaks and emergency situations, a single-dose study was launched at the beginning of 2014 in Bangladesh. IVI, with iccdr,b, will assess if one dose of the vaccine is sufficient to provide protection against cholera. • New partnership with Incepta Vaccines for cholera and typhoid vaccines for Bangladesh. IVI will collaborate with the Bangladeshi manufacturer, Incepta Vaccines, on the clinical development and production of the oral cholera vaccine and typhoid conjugate vaccine. The partnership was initiated with technology transfers made by IVI to Incepta in 2014. Cholera and typhoid are significant public health problems in Bangladesh. Having a local manufacturer committed to providing cholera and typhoid vaccines will certainly augment the fight against these diseases. • Conclusion of the Typhoid Surveillance in Africa Program (TSAP). Since 2011, IVI has been coordinating standardized typhoid surveillance among field sites in 10 sub-Saharan African countries in order to generate data on the epidemiology of typhoid in Africa. In 2014, TSAP wound down, and findings from the multi-year surveillance were analyzed for publication. The findings will be published in a supplement of Clinical Infectious Diseases in 2015. IVI is moving on to the next research phase post-TSAP, which will look at severe typhoid in Africa. • New field sites and studies for the Dengue Vaccine Initiative (DVI). Under DVI, IVI has been conducting disease burden studies in Thailand, Vietnam and Colombia. In 2014, IVI expanded its dengue research to new countries in Africa (for the first time) and Asia. New studies were initiated in Burkina Faso, and preparations were made for the launch of field sites in Gabon, Kenya and Cambodia. INTERNATIONAL VACCINE INSTITUTE 13 Science for Impact 14 ANNUAL REPORT 2014 Our Progress in 2014 Cholera Since 2002, IVI, with partners in Korea, Bangladesh, the United States, India, Sweden and Vietnam, has been leading efforts to accelerate the development and introduction of safe, effective and affordable oral cholera vaccines to fight endemic and epidemic cholera. What is Cholera? Cholera is a serious cause of acute watery diarrhea around the world, infecting three to five million people and responsible for about 100,000 deaths annually. It affects both children and adults and can kill within hours if not properly treated. Cholera is a disease of poverty and strikes in settings where there is overcrowding and limited access to safewater and sanitation. As recently seen in Haiti, explosive and deadly outbreaks can occur following natural disasters and humanitarian crises when systems break down. A New Solution: An Oral Cholera Vaccine for Global Use Improvements in water quality, hygiene, and sanitation have long been the tools to prevent and control cholera. While effective, these are longterm measures and difficult to implement in low-income countries with limited resources. Oral cholera vaccines are an effective tool that reaps short- to medium- term results, especially during outbreaks when immediate action is needed. Back in the early 2000's Vietnam had already developed and licensed an oral cholera vaccine. However, in order for this vaccine to be used internationally, it had to be modified to meet the requirements set by the World Health Organization (WHO). Therefore, IVI reformulated the vaccine in order to comply with WHO standards. The technology for the modified vaccine was then transferred back to Vabiotech in Vietnam and to a manufacturer in India (Shantha Biotechnics). In INTERNATIONAL VACCINE INSTITUTE 15 Cholera Vietnam, the modified vaccine (mVORC-VAXⓇ) was licensed and is now being used nationally. Meanwhile in India, IVI collaborated with Shantha Biotechnics and other partners to perform clinical trials to demonstrate the vaccine was safe and effective and obtain approval from the national regulatory authority. Since the vaccine also needed to be affordable for use in low-income countries, IVI negotiated with Shantha to establish a special public-sector price. The pivotal trials conducted in Kolkata showed that two doses of oral cholera vaccine provided protection for up to five years. The vaccine was licensed in India as Shanchol™ in 2009 and IVI worked closely with the manufacturer to get the vaccine WHO-prequalified in 2011. This was a major achievement for IVI. To date, only three vaccines developed through product development partnerships (PDPs) have been WHO-prequalified, and Shanchol™ is one of them. The Work Continues IVI continues to work on optimizing Shanchol™ for use in developing countries. For example, Shanchol consists of a two-dose regimen, but a single-dose regimen would be logistically easier to administer in 16 ANNUAL REPORT 2014 campaigns for outbreaks and emergency situations. Therefore, a singledose study was launched in Bangladesh at the beginning of 2014. IVI, with iccdr,b, will assess if one dose of the vaccine is sufficient to provide protection against cholera. IVI also continues to work in Vietnam, such as supporting efforts to have the Vietnamese national regulatory authority recognized by the WHO. This recognition will help pave the way for WHO prequalification of mORC-VAX. Increasing Access IVI recognized that having more than one manufacturer of the oral cholera vaccine for the global market would ensure a reliable supply at an affordable price. EuBiologics, a Korean company, was selected as a second manufacturing partner and in 2010 IVI transferred the technology for production and quality control of inactivated oral cholera vaccine to them. IVI has worked with Eubiologics to perform the necessary trials for licensure in Korea and to obtain subsequent WHO prequalification. As part of the global access agreement between the two parties Eubiologics will provide high quality affordable vaccine for public sector use in resource poor countries. Substantial progress was made in 2014 on the EuBiologics vaccine, EuvicholⓇ. The vaccine is poised to receive export licensure from the Korean Ministry of Food and Drug Safety in 2015, paving the way for its subsequent application to WHO for prequalification. Once WHO prequalification is achieved the vaccine can be sold through UNICEF to the global market highlighting the major contribution of Eubiologics and the Republic of Korea to the fight against the burden of cholera. We gratefully acknowledge the Governments of the Republic of Korea and Sweden, Bill & Melinda Gates Foundation, LG Electronics, Kia Motors, and Kim & Chang for their support. In 2014, IVI began working with a new partner, Incepta Vaccine Ltd, a Bangladeshi company, for the technology transfer and clinical development of the oral cholera vaccine. Since cholera is endemic in Bangladesh, there is great need for a domestically produced oral cholera vaccine. The partnership with Incepta will help reduce the burden of cholera in Bangladesh. We gratefully acknowledge the Governments of the Republic of Korea and Sweden, Bill & Melinda Gates Foundation, LG Electronics, Kia Motors, and Kim & Chang for their support. Demonstrating impact A global oral cholera vaccine stockpile was established in late 2013 financed by Gavi, the Vaccine Alliance and managed by WHO and other partners. The purpose of the stockpile is to expedite the delivery of cholera vaccines for rapid outbreak response in emergencies and crisis situations. The stockpile was used for the first time in 2014 to combat a cholera outbreak in South Sudan. While perceptions have been changing about using a vaccine to fight cholera, more evidence is needed to demonstrate the impact of vaccination and to generate demand for the oral cholera vaccine. IVI has been collaborating with local health authorities and partners on the introduction of the oral cholera vaccine in Malawi, Ethiopia, India and Bangladesh to provide practical evidence that cholera vaccination works, is feasible, and is well-accepted by the community. In 2014, IVI continued to provide technical support to icddr,b for the introduction of the vaccine in Bangladesh. In addition, we have been preparing for pilot vaccination campaigns in Ethiopia and Malawi slated for launch in early 2015. Those projects are supported by LG Electronics and Kia Motors respectively. In late 2014, Shanchol was approved for use in the pilot campaign by the Ethiopian national regulatory authority after a clinical trial showed that it was safe and immunogenic in the Ethiopian population. Cholera control remains a work in progress, and IVI is commited to increasing vaccine supply and advocating for the use of the vaccine - so that all communities at risk are protected against this deadly disease. INTERNATIONAL VACCINE INSTITUTE 17 Enteric Fever IVI is using the experiences and lessons learned from its successful work in cholera to accelerate the development and delivery of a new vaccine against enteric fever. As with cholera, IVI is using a global partnership approach and is collaborating with partners from Korea, Indonesia, Bangladesh, and the United States to make a new vaccine accessible and available to populations that desperately need it. What is Enteric Fever? Enteric fever (more commonly known as typhoid fever) is a bacterial disease caused by Salmonella Typhi. It is spread through the ingestion of food or drink contaminated by the feces or urine of infected people. It is usually characterized by fever, headache, constipation, and malaise, but it has few symptoms that reliably distinguish it from other infectious diseases, which makes it difficult to diagnose and treat. Symptoms range from mild to severe, and can progress to death or be associated with a chronic carrier state. Because it is difficult to diagnose typhoid, estimates for the numbers of typhoid cases and deaths vary but 21 million cases of typhoid fever and 200,000 deaths are estimated to occur worldwide. Like cholera, it occurs in low-income settings with poor sanitation and hygiene, and lack of clean water. Infants and young children in particular are at risk. 18 ANNUAL REPORT 2014 A New Hope in the Form of a Vaccine IVI has completed development of a typhoid conjugate which consists of the Vi polysaccharide purified from Salmonella Typhi chemically conjugated to diphtheria toxoid (DT). Compared with un-conjugated Vi typhoid vaccines, this new typhoid conjugate vaccine (Vi-DT) promises to protect infants less than two years of age as well as young children against typhoid fever and provide a longer duration of protection. IVI has now transferred the technology for production and quality control of Vi-DT to three manufacturing partners and will now assist with the development of a clinical plan and performance of clinical trials required for licensure and WHO prequalification. As with all of IVI’s vaccine technology transfer partnerships global access agreements have been signed to ensure high quality affordable vaccine for use in publicsector markets. In 2014, IVI worked with two of our partners - SK Chemicals of Korea and BioFarma of Indonesia - to finalize clinical development plans and it is anticipated that the clinical trials with both companies will begin in 2016. In addition, Vi-DT technologies were transferred to Incepta Vaccine Ltd of Bangladesh in 2014 and IVI has been active in assisting scale up in their plant in Bangladesh. IVI has also been developing a functional serum bactericidal assay that should help answer questions concerning vaccine efficacy and correlates of protection and hopefully will simplify the pathway to licensure and WHO prequalification of IVI’s and other Vi conjugate vaccines. Having three manufacturers of the typhoid vaccine will help ensure a sufficient and cost-competitive supply for the global market. The vaccine is expected to be licensed and WHO prequalified in readiness for global use as early as 2019. A New Vaccine to Combat Typhoid and Paratyphoid Fever IVI is also developing a bivalent enteric fever vaccine to protect against typhoid and paratyphoid fever. There is reportedly a high burden of paratyphoid fever in South Asia therefore a single vaccine that can protect against both diseases would be extremely beneficial. IVI has developed new conjugation methodologies for the Paratyphoid conjugate. A bivalent (Typhoid/Paratyphoid A) candidate is in the preclinical phase, and if all goes well, technology transfer to a manufacturer will be made soon. We gratefully acknowledge the Governments of the Republic of Korea and Sweden, and the Bill & Melinda Gates Foundation for their support. Assessing the True Burden of Disease Since 2011, IVI has been conducting typhoid surveillance among a network of field sites in thirteen sites in ten sub-Saharan African countries through the Typhoid Surveillance in Africa Program (TSAP). While anecdotes suggest that typhoid is a problem in Africa, there were limited scientific data to back up those claims. TSAP, funded by the Bill & Melinda Gates Foundation, was established to generate the scientific data on the epidemiology of typhoid in Africa. In 2014, we concluded TSAP and started analyzing and writing up the findings from the multi-year surveillance for publication. Our results show a significant burden of typhoid in Ghana, Kenya, Madagascar and Burkina Faso; yet non-typhoidal Salmonella infection may be more of a problem than S. Typhi, particularly in Plasmodium falciparum malariaendemic settings. In addition, multi-drug resistance is a concern and severe typhoid cases are seen in rural settings. The findings will be published in a supplement of Clinical Infectious Diseases in 2015. Based on these findings, IVI is moving on to the next research phase, which will look at in more detail the outcomes of severe typhoid cases in Africa. This data will help inform donors, governments and policymakers in making decisions about investing in the new typhoid vaccine when it is ready. Furthermore, IVI has been synthesizing evidence to support the introduction of the new vaccine by estimating the economic burden of typhoid, vaccine demand and supply forecast, and vaccination impact. We have also been developing a disease transmission model, which will help with estimations and forecasting. We gratefully acknowledge the Governments of the Republic of Korea and Sweden, and the Bill & Melinda Gates Foundation for their support. Enteric Fever INTERNATIONAL VACCINE INSTITUTE 19 Dengue IVI leads the international consortium known as the Dengue Vaccine Initiative (DVI), whose mission is to encourage the development and consideration of vaccines to prevent dengue. DVI lays the groundwork for dengue vaccine decision-making and introduction in endemic areas. DVI members are: • IVI - lead the Consortium and is responsible for field studies that generate evidence on burden of disease, as well as coordinating the Dengue Prevention Boards for the Americas region and the AsiaPacific region. • WHO Initiative for Vaccine Research (IVR) - lead in the development of information and guidance documents, and in regulatory training activities. • International Vaccine Access Center of Johns Hopkins University’s Bloomberg School of Public Health - lead activities related to the financing of dengue vaccine purchase including budget impact analysis and strategic demand forecasting. • Sabin Vaccine Institute- lead DVI’s coalition-building, advocacy, and communications activities. 20 ANNUAL REPORT 2014 What is Dengue? Dengue fever (also known as breakbone fever) is a debilitating and painful disease. Signs and symptoms include headache, skin rash, and muscle and joint pain. In some cases, dengue can lead to circulatory failure, shock, coma, and even death.Individuals who have been infected with dengue are more likely to contract severe dengue when infected again.There is no medication or cure. Dengue is a viral disease caused by one of four virus serotypes, which are spread to humans by mosquitoes (Aedes aegypti). Dengue is often found in urban areas in tropical and subtropical regions with many reported cases in Asia and Latin America. The WHO estimates there may be 50 million dengue infections worldwide every year. Currently dengue is endemic in over 100 countries, and in 2013, it was ranked by the WHO as the fastest spreading vector-borne viral disease with the potential to cause an epidemic in the world. Compared with other infectious diseases, dengue does not have a high mortality but it exerts a considerable economic burden. The cost of illness to society is high, from lost wages and decreased productivity to costs associated with medical expenses. Dengue Vaccines on the Horizon consideration for vaccine introduction. Dengue prevention efforts have usually focused on vector control but the development of dengue vaccines has accelerated dramatically in recent years. There are several vaccines in various stages of advanced development, with clinical trials currently underway. The frontrunner is Sanofi Pasteur’s live attenuated chimeric tetravalent vaccine that has been in Phase 3 trials. Several major regulatory meetings were held in 2014 as well. In 2013, DVI formed a group of regulators from seven countries with interest in the early adoption of dengue vaccines. The DVI regulatory group met twice in 2014. At a meeting in Beijing, the national regulatory authorities (NRAs) of five countries signed an agreement to cooperate on the joint evaluation of files or protocols of novel dengue vaccines. The group also met again in Jakarta, Indonesia with NRA representatives from Brazil, Colombia, Indonesia, Malaysia, Mexico, Philippines, and Thailand. They reviewed and agreed on more specific details of joint evaluations of clinical trial applications and of registration dossiers. DVI has been paving the way for introduction of the dengue vaccine through policy and access, regulatory, and advocacy activities. IVI for its part has been generating evidence on the disease and economic burden of dengue through field studies in Thailand, Vietnam, and Colombia. In 2014, IVI continued surveillance, serological surveys, and cost-of-illness survey in these countries. In addition, we initiated studies in Burkina Faso, and made preparations for the launch of new field sites in Gabon, Kenya and Cambodia in 2015. Two Dengue Prevention Board Meetings were convened in 2014 - one in Mexico City for the Latin Americas region in March, and one in Seoul for the Asia-Pacific region in November. The Americas meeting discussed the basis for the collaborative and integrated approaches to dengue prevention and control, while the Asia-Pacific meeting focused on a review of the vaccine development status and points for Finally, DVI continued to provide technical support to Instituto Butantan of Brazil and Vabiotech of Vietnam on development of their dengue vaccines, especially in process development, regulatory guidance, and capacity-building in clinical trials. This initiative is funded by the German Federal Ministry of Education and Research (BMBF). The Dengue Vaccine Initiative is supported by the Bill & Melinda Gates Foundation. It also receives support from the German Federal Ministry of Education and Research (BMBF), Takeda, and Sanofi Pasteur. Dengue INTERNATIONAL VACCINE INSTITUTE 21 In the Pipeline: Research Highlights Discovering new vaccines with conjugation technology Based on work with the typhoid conjugate vaccine (Vi polysaccharide conjugated to diphtheria toxoid; Vi-DT), IVI has been developing a Vi conjugate technology platform and using it as a presentation vehicle for poorly immunogenic proteins. The concept is based on early observations that the Vi polysaccharide conjugated to a protein carrier enhances the response to the protein if the conjugate is constructed in a certain way, possibly causing slow release of the antigen resulting in a enhanced and prolonged immune response. Some preliminary conjugates that IVI is working on: • Vi-PspA Vi conjugated to PspA, a common pneumococcal protein expressed on the surface of Streptococcus pneumoniae strains • Rotavirus conjugate Vi conjugated to virus-like particles of rotavirus VP8; through a collaboration with the University of Queensland 22 ANNUAL REPORT 2014 • Hib-HBsAg conjugate Hib PRP conjugated to HBsAg (hepatitis B surface antigen) • Typhoid-malaria conjugate through a collaboration with the U.S. National Institutes of Health IVI is also looking into the possibility of developing a pediatric combination vaccine for developing countries. Combining several conjugates into a single vaccine product would reduce the number of pediatric doses, making it easier to fulfill the recommended childhood immunization schedule and to help increase vaccination coverage rates. This work is supported by the Governments of Sweden and the Republic of Korea (National Research Foundation of Korea and the Ministry of Education) and the Bill & Melinda Gates Foundation. New vaccine candidates against norovirus and Shigella IVI is also discovering new vaccines against norovirus and Shigella, both significant causes of enteric infections in the developing world. Norovirus is the most common cause of viral gastroenteritis in humans, affecting people of all ages. A vaccine is currently not available. Most human norovirus vaccine studies have focused on virus-like particles (VLPs) as the vaccine candidate, however in clinical trials,the efficacy of norovirus-like particles (noroVLP) has been shown to be only about 47 percent. IVI is studying the enhancement of the immunogenicity and efficacy of current VLP-based norovirus vaccines by evaluating the immunogenicity of noroVLP following mucosal administration. In addition, IVI is using a novel mucosal adjuvant based on a genetically engineered cholera toxin, called TCTA1, which shows promising levels of immunogenicity without toxicity. The data indicate that immunization of mice with via the mucosal route produced robust antibody responses specific to noroVLP, suggesting that administration of noro VLP via the mucosal route promoted induction of norovirus-specific antibody responses systemically and locally. Also, a significant boost in norovirus specific cellular immunity was shown following mucosal immunization with noroVLP compared with mice that received parenteral immunization. Additionally, co-administration of noroVLP with TCTA1T via the mucosal route generated a robust antibody response against norovirus. While preliminary, these results indicate that administration of TCTA1T-adjuvanted noroVLP via the mucosal route can increase vaccine efficacy by eliciting systemic immunity as well as local immunity in the gastrointestinal mucosa. However further studies are needed to establish proof of concept. Shigella infection (shigellosis) represents a major burden of diarrheal disease in infants and young children in developing countries. About 1.1 million people die from Shigella infections annually in developing countries, 60 percent of whom are children under 5 years old. Like norovirus, a vaccine is currently not available. There are challenges in developing a Shigella vaccine due to the wide genetic variation of the Shigella bacterium, which comprises of four species and more than 50 serotypes as specified by the composition of the surface polysaccharide O antigen. Due to the serotypic differences and increasing reports of antibiotic-resistant Shigella strains, the development of a universal Shigella vaccine is needed. To develop a universal vaccine, IVI has been working on the construction of a mutant Shigella bacterium in which the genetically modified bacterium expressesa shorter lipopolysaccharide (LPS) with one unit of O-antigen on the bacterial cell wall. This in turn increases the exposure of membrane antigens, including protein antigens that are conserved across different species and serotypes of Shigella. Thus, vaccination using genetically modified Shigella with enhanced exposure of common outer-membrane proteins could be an efficacious approach to developing a universal Shigella vaccine. Work is ongoing in murine challenge models to assess cross-protection and if the mutated construct can induce cytokine and humoral responses to Shigella. This work is supported by the Governments of Sweden and the Republic of Korea (National Research Foundation of Korea and the Ministry of Education). PROVIDE: Performance of oral rotavirus and poliovirus vaccines in developing countries PROVIDE is a research study funded by the Bill & Melinda Gates Foundation (BMGF) that seeks to understand the impact of tropical enteropathy on the immune response to oral vaccines. Tropical enteropathy is a disturbance in the intestinal lining that makes it difficult for the body to absorb nutrition and is often observed in children from low-income countries. It has also been observed that children from lowincome countries have a decreased immune response to oral vaccines compared with children from developed countries. This occurrence has significant implications for the impact of national vaccination programs. Understanding, treating or preventing tropical entropothy is critical to achieving maximal impact from vaccination. With India’s National Institute of Cholera and Enteric Diseases (NICED), University of Virginia, and University of Vermont, IVI has embarked on an observational study to see if there is a relationship between children with tropical enteropathy and those who do not respond well to oral INTERNATIONAL VACCINE INSTITUTE 23 polio and rotavirus vaccines. The study will also identify if maternal breast milk has a role in the child’s immune response to vaccines; how a child’s nutritional status is related to this problem; and whether some children with tropical enteropathy and those who do not respond well to oral polio and rotavirus vaccines. The study will also identify if maternal breast milk has a role in the child’s immune response to vaccines; how a child’s nutritional status is related to this problem; and if some children may be more likely to develop tropical enteropathy compared with others. The study enrolled 372 infants at the hospital study site in Kolkata, India. All infants, as part of their routine immunization, received the EPI vaccines, as well as the oral rotavirus vaccine (Rotarix). For the polio vaccine, infants were randomized into two groups with one group receiving the injectable polio vaccine (IPV) and the other group receiving the oral polio vaccine (OPV). All of the lab tests were conducted at the IVI /NICED Immune-monitoring laboratory. Preliminary analyses suggest that there is a poor immune response to oral rotavirus vaccines with immunogenicity less than 40 percent. Furthermore, there appears to be a negative correlation between maternal breast milk antibody titers and the infant’s immune response to vaccination, suggesting that breast milk antibodies may interfere with the infant’s gut immune response. Other factors such as infant’s age at enrollment, maternal BMI, maternal zinc supplementation and poor breast feeding were associated with the child’s antibody response to the rotavirus vaccine. Moving forward, polio immunogenicity data will be completed, and preliminary and secondary data analyses will be done. Additional biomarkers will be tested to identify the interference of tropical enteropathy, as well as the role of gut homing cells as a correlate of protection in rotavirus infection. Based on the PROVIDE data, IVI has initiated work on developing a rotavirus conjugate vaccine. The process development and clinical immunology teams are working together to develop an vaccine for developing countries. Policy and Economic Research: Developing evidence to support vaccine use IVI’s Policy and Economic Research (PER) focuses on promoting the use of evidence-based analyses for vaccine introduction. PER synthesizes evidence, conducts health economics studies, and develops transmission models to help with forecasting and estimations of vaccination impact and costing. It also disseminates evidence to national- and global-level 24 ANNUAL REPORT 2014 policymakers and donors to support deliberations on vaccine introduction. In 2014, an estimation of the economic burden of typhoid fever was conducted along with the synthesis of typhoid fever outcomes, vaccine demand and supply forecast, vaccination impact estimates, and the development of a transmission model. Some of these findings were presented in June and September 2014 to WHO’s Immunization and Vaccine- Related Implementation Research Advisory Committee (IVIR-AC) which reports to the WHO Strategic Advisory Group of Experts (SAGE) for future policy recommendations. An estimation of the typhoid fever burden in low- and middle-income countries was published in The Lancet Global Health. PER has been also working on developing an oral cholera vaccine delivery cost estimation tool and a transmission model to estimate cholera vaccination impact at global level. For dengue, PER has been conducting health economics studies in Thailand, Vietnam, and Colombia in collaboration with the Dengue Vaccine Initiative (DVI). New studies were launched for Burkina Faso, Gabon, and Cambodia. The findings from these studies will help make the case for dengue vaccine use. Biostatistics and Data Management IVI’s Biostatistics & Data Management conducts data management, statistical analyses, and transmission modeling of infectious diseases, which supports IVI’s field research. In 2014, the team helped the Dengue Vaccine Initiative (DVI) launch a mobile-based system using PDA devices and conduct data management training using internet applications at a field site in Burkina Faso during the peak of the Ebola virus crisis in West Africa. The use of internet applications in data management was a new approach and helped avoid delay of the study launch due to travel restrictions to Burkina Faso and political instability as a result of the Ebola crisis. This real-time data collection system using tablet devices is also being planned for IVI’s typhoid surveillance studies in Africa. Finally, IVI, in collaboration with WHO’s Global Vaccine Safety Initiative (GVSI), developed a new software tool for collecting and processing information on adverse events following immunization (AEFI) to promote internationally harmonized tools and methods to support vaccine safety. Known as the Vaccine Adverse Events Information Management System (VAEIMS), this tool was pilot-tested in Sri Lanka and evaluated for its ability to transfer AEFI data from health outposts into a central database for processing and conversion of raw data to information for action. Based on its success, Sri Lanka has decided to use it at the national level. VAEIMS will soon be adapted for global use. INTERNATIONAL VACCINE INSTITUTE 25 Building Success Mr. Bum Soo Lee and his family at IVI Communications & Advocacy The Deadly Beauty Campaign - Enteric Fever IVI’s Communications & Advocacy (C&A) aims to raise awareness of the institute and to mobilize resources and support. Some C&A highlights in 2014 include the IVI school visitors program that allows students to visit the institute and to learn more about vaccines and vaccination. IVI welcomed 700 students in 2014. In July, IVI launched the Choose Your World campaign in partnership with NYK Media. The campaign was centered on a video which shows the difference a small donation can make in supporting vaccine research and development. More information on the campaign can be found at http://Choose.ivi.int. IVI also launched Deadly Beauty, a social media campaign, to raise awareness about neglected infectious diseases. The concept involved depicting germs responsible for diseases such as Ebola and cholera as body art on models. The campaign was featured in journals and blogs including BoredPanda.com, Jyllands-Posten, and FashionWaltz.com. This campaign was made possible with in-kind support from Alec Kim Photography, Scorpio Body Painting, MarieM Beauty, Westage& Co., and The C R O C H E. Further information can be found at: https://www.facebook.com/DeadlyBeautyCampaign. The year 2014 also marked the launch of the IVI International Photo Contest with the theme of children around the world. The contest saw 4,741 admissions from countries around the world. The top 60 photos were selected by a panel of professional photographers and displayed at an exhibition at Seoul City Hall. The contest was run with support from Yanghyun Foundation and the Korean Ministry of Education. To see the winners, please visit: http:// iviphoto.org/eng In September, IVI launched the Kids Helping Kids Program (KiKi), an educational program targeting Korean school children. The program teaches students about the importance of charity and being a global citizen, while at the same time providing basic science and health education (e.g., how germs can spread and how diseases can be prevented hand washing and immunization). The KiKi Program was supported by Yanghyun Foundation and the Korean Ministry of Education. The program will be rolled out in a select number of schools as a pilottest in 2015. Finally 2014 marked the signing of Korean actor Mr. Bum Soo Lee as the IVI Goodwill Ambassador. Mr. Lee said, “It is my great honor to have the opportunity to support IVI, which is striving to improve the health of children who are left behind the benefits of public health,” adding, “I will do my best to ensure that more (Korean) people can sympathize with and extend support to IVI’s noble mission” 26 ANNUAL REPORT 2014 Building Capacity IVI’s International Advanced Course on Vaccinology in the Asia-Pacific Region marked its fourteenth year in 2014. The annual course is a five-day advanced course on vaccinology held in May at IVI’s headquarters in Seoul. It aims to provide vaccine professionals from around the globe a comprehensive overview of vaccinology. During the course, AVC faculty consisting of over 30 international experts, lecture on topics that span from basic epidemiology and immunobiology to vaccine development to vaccine introduction to use and communications. Seventy trainees from 20 countries including Bhutan, China, Nepal, Sudan, Switzerland, Thailand and Vietnam participated in the course. The participants were a diverse mix of scientists, public health officials, and policymakers from private and public sectors, including 14 fellows - IVI annually awards competitive fellowships to individuals with demonstrated financial need. The course covered basic epidemiology and immunobiology topics. The course then proceeded through topics related to taking a vaccine from development to the field. The week ended with lectures on vaccine communications and immunization in specialized groups. The course was supported by GlaxoSmithKline, Pfizer, Korea Exchange Bank (KEB) Foundation, and the ExportImport Bank of Korea. INTERNATIONAL VACCINE INSTITUTE 27 Vaccines for Children 28 ANNUAL REPORT 2014 Board of Trustees Members-at-large Prof. Adel A.F. Mahmoud (Chair) Professor Department of Molecular Biology and the Woodrow Wilson School of Public and International Affairs, Princeton University U.S.A. Mr. George Bickerstaff (Treasurer & Chair of Finance Committee) Partner and Managing Director, M.M. Dillon & Co. U.S.A Prof. Juhani Eskola Director General National Institute for Health and Welfare (THL) Finland Dr. J. Joseph Kim President & CEO Inovio Pharmaceuticals U.S.A Prof. Fred N. Binka Vice Chancellor University of Health and Allied Sciences Ghana Dr. George R. Siber (Chair of Scientific Committee) Chief Scientific Officer ClearPath Vaccines Representatives of WHO, UNDP, and Host Country (Republic of Korea) Dr. Shin Young Soo Regional Director WHO Western Pacific Regional Office (WPRO) Philippines Mr. Romulo Garcia Senior Adviser Regional Bureau for Asia and the Pacific, UNDP New York Mr. Yoo Dae-jong Director General International Organizations Bureau Ministry of Foreign Affairs Republic of Korea Dr. Kang Young-Soon Director General International Cooperation Bureau Ministry of Education Republic of Korea Representatives of State Parties to Establishment Agreement Dr. Viveka Persson - Vice Chair & Chair of Governance & Nominating Committee Uredare/Senior Project Manager Swedish National Agency for Higher Education Sweden Ex-officio Director General International Vaccine Institute INTERNATIONAL VACCINE INSTITUTE 29 Scientific Advisory Group Dr. Robert E. Black (Chair) Professor - International Health John Hopkins University, School of Hygiene & Public Health U.S.A. Dr. Duane J. Gubler Professor Program on Emerging Infectious Diseases Duke-NUS Graduate Medical School Singapore Dr. Gagandeep Kang Professor and Head The Wellcome Trust Research Laboratory India Dr. Byoung S. Kwon Endowed Investigator National Cancer Center Republic of Korea Dr. Claudio F. Lanata Senior Researcher Instituto de Investigacion Nutricional IIN Science Director US Navy Medical Research Unit 6 Professor School of Medicine, Peruvian University of Applied Sciences UPC Peru Dr. Jacques Louis Professor Emeritus Faculty of Medicine University of Lausanne, Switzerland and Institut Pasteur, Paris Director Emeritus Department of Parasitology and Mycology, Institut Pasteur, Paris (2003-2008) France Dr. G. Balakrish Nair Executive Director Translational Health Science and Technology Institute India 30 ANNUAL REPORT 2014 Dr. Pearay L. Ogra John Sealy Distinguished Chair Professor and Chairman [Emeritus] Department of Pediatrics State University of New York at Buffalo Children's Hospital U.S.A. Dr. David A. Sack Professor, Department of International Health Johns Hopkins University Bloomberg School of Public Health U.S.A. Dr. Rho Hyun Seong Professor School of Biological Sciences, College of Natural Sciences Seoul National University Republic of Korea Dr. Peter Smith Professor Department of Epidemiology and Population Health London School of Hygiene & Tropical Medicine U.K. Major Donors in 2014 Core funding to IVI is provided by the governments of the Republic of Korea and Sweden. Public- and private-sector organizations and individuals also provide support, both monetary and in-kind, for the Institute’s research and programs. Prominent organizations and individuals in Korea provide support due to efforts of the Korea Support Committee for IVI (KSC). While there are too many donors to list here, their generosity is deeply appreciated. To see the full list of IVI donors, please refer to the IVI website: http://www.ivi.int. aSSIST CEO Forum Association of Research & Development for Experience Education Bill & Melinda Gates Foundation (BMGF) BOAZ ENT Clinic Network Chong Kun Dang Kochun Foundation Clue Coaching and Career Community Chest of Korea Coreana Cosmetics Diplomacy Magazine Export-Import Bank of Korea German Federal Ministry of Education and Research (BMBF) GlaxoSmithKline Biologicals KfW Development Bank Kia Motors Kim & Chang Committee for Social Contributions Korea Centers for Disease Control & Prevention Korea Exchange Bank Foundation Korea Fashion Association Korea Health Industry Development Institute Korea Research Institute of Bioscience and Biotechnology (KRIBB) Korea Support Committee for the IVI (KSC) LG Electronics Ministry of Education (MOE), Republic of Korea Ministry of Foreign Affairs (MOFA), Republic of Korea National Research Foundation of Korea (NRF) Pfizer, Inc. Samjin Globalnet Co., Ltd. Sanofi Pasteur Seoul Dairy Cooperative Sky 72 Golf & Resort Smart Optech Swedish International Development Cooperation Agency (Sida) Takeda Pharmaceutical Company University of Bielefeld (UOB) World Health Organization (WHO) Yanghyun Foundation INTERNATIONAL VACCINE INSTITUTE 31 Korea Support Committee for the IVI (KSC) Established in 1998, the KSC is a nonprofit organization that mobilizes support in Korea for IVI. The Committee consists of prominent leaders from government, industry, and academia in Korea. For more information, please visit: http://www.ivi.int/ksc. President & Chair of the Board Prof. Cho Dong-Sung, Professor Emeritus, Seoul National University Vice Presidents Prof. Park Sang-Chul, Executive Vice President, Well Aging Research Center, Samsung Advanced Institute of Technology Dr. Rhee Byung-Geon, President, Green Cross Holdings, Co. Executive Advisor Prof. Cho Wan-Kyoo, Former President, Bioindustry Association of Korea/Former President, Seoul National University / Former Minister of Education 32 ANNUAL REPORT 2014 Chief Advisor Prof. Park Sang-Dai, Professor Emeritus, Seoul National University Legal Advisor Mr. Choi Sang-Yup, Lawyer, Former Minister of Justice / Vice Prosecutor-General Executive Director Prof. Hong Seung Hwan, Professor, Seoul National University College of Natural Sciences Advisors Mr. Chae Hee-Byung, President, Dongjin Chemical Co., Ltd. Dr. Chae Young Bog, Former Chairman, Gyeong Gi Bio-Center / Former Minister of Science & Technology Dr. Chung Won-Shik, Chairman, The Yuhan Foundation / Former Prime Minister Mr. Kang Choong Hyun, Chairman, Samjin Globalnet Co., Ltd. Mr. Kang Shin-Ho, Chairman, Dong-A Socio Group Mr. Kim Jaison, Publisher, The Samtohsa / Founding President of KSC / Former Speaker of General Assembly Dr. Kim Kee-Hyong, Honorary President, Korea Ceramics Culture Promotion Society / Former Minister of Science & Technology Prof. Kim Nak Doo, Professor Emeritus, Seoul National University College of Pharmacy Prof. Kim Sang-Joo, Former President, the National Academy of Sciences, Republic of Korea Prof. Kim Si Joong, Chairman, The Science-Technology Forum / Former Minister of Science & Technology Prof. Kwon E. Hyock, Professor Emeritus & Former President, Seoul National University / Former Minister of Education / Public Health / Environment Dr. Lee Gil-ya, President, Gachon Gil Foundation Prof. Lee Ho-Wang, Former President, the National Academy of Sciences, Republic of Korea Mr. Lee Kyu Hyung, Advisor, Samsung Research Institute, Former Ambassador of the Republic of Korea in China and Russia, Former Deputy Minister of MOFA Prof. Lee Sang Sup, Professor Emeritus, Seoul National University College of Pharmacy Mr. Lee Se-Ung, Chairman, Shin Il Co. / Chairman, Seoul Cyber University / Former President, Korea National Red Cross Prof. Park Soo-Gil, Chair Professor, Korea University / Former Permanent Representative of the Republic of Korea to the UN Dr. Rhee Shang-Hi, Chairman, Greenlife Intellectual Network, Former President, Korea Patent Attorneys Association / Former Minister of Science & Technology Prof. Son Bong Ho, Chairman, Korea Community Sharing Campaign, Professor Emeritus, Seoul National University Prof. Yoo Chong-Ha, Chair Professor, Graduate School of International Studies, Sogang University / Former President, Korea National Red Cross / Former Minister of Foreign Affairs & Trade Dr. Yoon Hong-Geun, Chairman & CEO, GENESIS BBQ Group Prof. Yu Jae-Cheon, Former President, Sangji University Mr. Won Dae Yunn, Chairman, Korea Fashion Association Board of Trustees Mr. Auh Jin, President, Ahn Gook Pharm. Mr. Chi Chang-Hoon, President & CEO, Korean Air Lines Dr. Choi Davis, President, Korea Vaccine Co., Ltd. Mr. Choo Hak-Yoo, President, Dong Woo Chem. Corp, Mr. Chun Hong Jae, CEO, Chun Loss Prevention Co., Ltd. INTERNATIONAL VACCINE INSTITUTE 33 Dr. Chung Chan Bok, President & CEO, Bioland Prof. Chung Kil Saeng, Former President, The Korean Academy of Science Technology; Emeritus & Former President, Konkuk University Mr. Chung Pal Do, Chairman, Korealand Co. Prof. Huh Kap Bum, Professor Emeritus & Former Dean, Yonsei University College of Medicine Mr. Jeffrey D. Johns, Chairman, Partners for the Future Foundation Mr. Kang Shin Jang, President, Monaissance Mr. Kim Duck Sang, CEO, Sartorius Korea Biotech Co., Ltd. Ms. Kim Eun-Sun, Chairman, Boryung Pharm. Prof. Kim Ki Seok, Professor, Seoul National University College of Education Mr. Kim Kyong Ho, Chairman, Hankyong Instrument & ENG Co., Ltd Prof. Kim Kyungjin, Professor, Department of Brain Science, Daegu Gyeongbuk Institute of Science & Technology Prof. Kim Sun Young, Professor, Seoul National University College of Natural Sciences Mr. Kim Young-Kee, President, Korea Industrial Safety Association Mr. Kim Peter Pumsoo, Chairman, InnoS & S Co., Ltd. Mr. Kim Sun Ki, President, Bio-Medical Science Co., Ltd Mr. Kim Young Je, President & CEO, Sky 72 Golf Club Mr. Lee Doung Young, CEO, Marketing Production, Seoul Dairy Cooperative Mr. Lee Jae Hoo, Senior Partner, Kim & Chang Mr. Lee In Jung, President & CEO, Taein Co., Ltd. Dr. Park Mahnhoon, CEO, SK Chemical Life Science Biz Ms. Lee Kyung Ja, Chairman, Association of Research & Development for Experience Education Mr. Lee Suk Ho, Former President, Ulsan Broadcasting Corp. Prof. Lee Young Soon, Professor Emeritus, Seoul National University Dr. Limb Thok-Kyu, Chairman, Magazine "Diplomacy" Mr. Moon Kyung Ahn, President & CEO, Volvik Dr. Oh Tae Kwang, President, Korea Research Institute of Bioscience and Biotechnology Prof. Paek Domyung, Professor, Seoul National University Graduate School of Public Health Prof. Park Kyung A, Professor, Yonsei University College of Medicine Mr. Park Nam Seo, CEO, Sanha Engineering & Construction Co. Prof. Song Jin Won, Professor, Korea University College of Medicine Mr. Stanley Cho, CEO, Smart Optech Mr. Shin Hyun Il, Chairman, Bomoon Co. Dr. Yang Yoon Sun, CEO & President, MEDIPOST Prof. Yim Jeong-bin, Chair Professor, Soon Chun Hyang University Mr. Yoo Myung Hwan, Chairman, Global Yoo Myung Co., Ltd. Dr.Yoon Eun Key, President, Korea Collaboration Association, Chair Professor, aSSIST (Seoul School of Integrated Science & Technology) Dr. Yoon Kang Jun, President, St. Peter’s Hospital Mr. You Kyung Nam, CEO, Liftec Co., Ltd. Auditors Mr. Kim Yong-Won, Partner, Samil PricewaterhouseCoopers Prof. Seong Rho Hyun, Dean for Research Affairs, & Professor, Seoul National University College of Natural Sciences 34 ANNUAL REPORT 2014 INTERNATIONAL VACCINE INSTITUTE 35 Major Partners in 2014 Agence de Medecine Preventive (AMP), France Hallym University, Republic of Korea Ajou University, Republic of Korea Hanyang University, Republic of Korea Armauer Hansen Research Institute (AHRI), Ethiopia icddr,b, Bangladesh AVIR Green Hills Biotechnology AG Incepta Vaccine Ltd., Bangladesh Bandim Health Project Indian Council of Medical Research, India Bangladesh Institute of Child Health, Bangladesh Institut Pasteur, Cambodia Beams Biotechnology Co., Ltd. Institut Pasteur, Korea Bernhard Nocht Institute for Tropical Medicine, Germany Institut Pasteur, Senegal Bharat Biotech, India Institut Superieur des Sciences de la Population (ISSP), Burkina Faso BioFarma, Indonesia Instituto Butantan, Brazil Bio-Korea, Republic of Korea Johns Hopkins University-International Vaccine Access Center (IVAC), USA Busan University, Republic of Korea Catholic University, Republic of Korea Celltrion, Republic of Korea Centre de Recherches Medicales de Labarene, Gabon Centre Muraz, Burkina Faso Chonbuk National University, Republic of Korea Chonnam University, Republic of Korea Christian Medical College, India Chungnam National University, Republic of Korea Developing Countries Vaccine Manufacturers Network (DCVMN) Coalition against Typhoid Directorate of Health Services, Department of Health and Family Welfare, State Government of Orissa, India Duke University Medical Center, USA Emory University, USA Ethiopian Health and Nutrition Research Institute, Ethiopia Eubiologics, Republic of Korea John Snow, Inc., USA Kangwon National University, Republic of Korea Kenya Medical Research Institute, Kenya Kilimanjaro Christian Medical Centre, Tanzania Konkuk University, Republic of Korea Korea Center for Disease Control, Republic of Korea Korea Institute of Tuberculosis, Republic of Korea Korea National Institute of Health (KNIH), Republic of Korea Korea Research Institute of Bioscience and Biotechnology (KRIBB), Republic of Korea Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana Kyunghee University Mahidol University, Thailand Metrosalud ESE / Unidad Hospitalaria communa Santa Cruz, Medellin, Colombia Ministry Of Food and Drug Safety, Republic of Korea Ewha Womans University, Republic of Korea Ministries of Health (Ethiopia, Kazakhstan, Kyrgyzstan, Malawi, Mongolia, Sudan) Fred Hutchinson Cancer Research Center Ministries of Public Health (Brazil, Colombia, Thailand) Gavi, the Vaccine Alliance, Switzerland Ministry of Health and Population, Nepal Global Health Investment Fund, USA National Center for Communicable Diseases, Ulaanbaatar, Mongolia Green Cross, Republic of Korea National Institute for Communicable Diseases (NICD), South Africa Group for Technical Assistance, Nepal National Institute of Cholera & Enteric Diseases (NICED), India 36 ANNUAL REPORT 2014 National Institute of Hygiene and Epidemiology (NIHE), Vietnam University of Melbourne, Australia National Institutes of Health (NIH), USA University of Ouagadougou, Burkina Faso Nihon University, Japan University of Oxford, UK Oromia Regional Health Bureau, Ethiopia University of Queensland, Australia Oxford Economic Forecasting, United Kingdom University of Vermont, USA Pan American Health Organization (PAHO) University of Virginia, USA PATH, USA University of Wisconsin, USA Pohang University of Science and Technology (POSTECH), Republic of Korea Vabiotech, Vietnam Programa de Estudio y Control de Enfermedades Tropicales (PECET), Universidad de Antioquia, Medellin, Colombia Walter Reed Army Institute of Research (WRAIR), USA Regional Medical Research Centre, Bhubaneswar, Orissa, India Sabin Vaccine Institute, USA Sanofi Pasteur, France Scientific Research Center for Epidemiological Expertise and Monitoring, Almaty, Kazakhstan Vaccine Technologies, Inc. (VTI) Washington University, USA Wellcome Trust Sanger Institute, UK WHO Department of Reproductive Health and Research WHO Initiative for Vaccine Research (IVR) WHO Programme for Immunization Preventable Diseases (IPD), Nepal Secretaria de Salud, Medellin, Colombia WHO Regional Office for Europe (EURO) Sejong University, Republic of Korea WHO Regional Office for South-East Asia (SEARO) Seoul National University, Republic of Korea WHO Regional Office for the Western Pacifi (WPRO) Shantha Biotechnics, India World Health Organization (WHO) SK Chemicals, Republic of Korea Yonsei University, Republic of Korea Stanford University, USA Takeda Pharmaceutical Company Limited, Japan Technical University of Berlin (TUB), Germany Transgovernment Enterprise against Pandemic Influenza of Korea (TEPIK) UNICEF, Nepal United States Centers for Disease Control and Prevention (CDC), USA Universidad Industrial de Santander, Colombia University of Alabama at Birmingham, USA University of Antananarivo, Madagascar University of Antioquia, Colombia University of Florida, USA University of Gezira, Sudan University of Gothenburg, Sweden INTERNATIONAL VACCINE INSTITUTE 37 2014 Scientific Publications 1. [No authors listed]. Typhoid fever surveillance and vaccine use, South-East Asia and Western Pacific Regions, 2009-2013. Wkly Epidemiol Rec 2014/Oct/03; 89(40): 429-39. 2. Ali A, An SJ, Cui C, Haque A, Carbis R. Synthesis and immunogenicity evaluation of Salmonella enterica serovar Paratyphi A O-specific polysaccharide conjugated to diphtheria toxoid. Hum Vaccin Immunother 2014/Mar; 10(6): 1494-8. 3. Amarasinghe A, Bhola AK, Halstead SB. Uncovering dengue in India: morbidity estimates. Global Journal of Medicine and Public Health 2014; 3(3) 4. Aye KS, Charngkaew K, Win N, Wai KZ, Moe K, Punyadee N, Thiemmeca S, Suttitheptumrong A, Sukpanichnant S, Prida M, Halstead SB. Pathologic highlights of dengue hemorrhagic fever in 13 autopsy cases from Myanmar. Hum Pathol 2014/Jun; 45(6): 1221-33. 5. Baik YO, Choi SK, Kim JW, Yang JS, Kim IY, Kim CW, Hong JH. Safety and immunogenicity assessment of an oral cholera vaccine through phase I clinical trial in Korea. J Korean Med Sci 2014/Apr; 29(4): 494-501. 6. Bajracharya D, Khan MI, Pach A 3rd, Shrestha P, Joshi N, Upreti SR, Wierzba T, Puri M, Sahastrabuddhe S, Ochiai RL. 25 years after vi typhoid vaccine efficacy study, typhoid affects significant number of population in Nepal. PLoS One 2014/Jan/06; 9(1): e77974. 7. Begum YA, Baby NI, Faruque AS, Jahan N, Cravioto A, Svennerholm AM, Qadri F. Shift in phenotypic characteristics of enterotoxigenic Escherichia coli (ETEC) isolated from diarrheal patients in Bangladesh. PLoS Negl Trop Dis 2014/Jul/17; 8(7): e3031. 8. Cassetti MC, Halstead SB. Consultation on dengue vaccines: progress in understanding protection, 26-28 June 2013, Rockville, Maryland. Vaccine 2014/May/30; 32(26): 3115-21. 9. Chang SY, Ko HJ, Kweon MN. Mucosal dendritic cells shape mucosal immunity. Exp Mol Med 2014/ Mar/14; 46: e84. 38 ANNUAL REPORT 2014 10. Chattaway MA, Jenkins C, Rajendram D, Cravioto A, Talukder KA, Dallman T, Underwood A, Platt S, Okeke IN, Wain J. Enteroaggregative Escherichia coli have evolved independently as distinct complexes within the E. coli population with varying ability to cause disease. PLoS One 2014/Nov/21; 9(11): e112967. 11. Cheon IS, Park SM, Lee HJ, Hong JE, Ji SY, Shim BS, Kim KH, Heo PS, Kim YY, Jung HJ, Ka H, Han SH, Song M, Yun CH. Functional characteristics of porcine peripheral T cells stimulated with IL-2 or IL-2 and PMA. Res Vet Sci 2014/Feb; 96(1): 54-61. 12. Cheon IS, Shim BS, Park SM, Choi Y, Jang JE, Jung DI, Kim JO, Chang J, Yun CH, Song MK. Development of safe and effective RSV Vaccine by modified CD4 epitope in G protein core fragment (Gcf). PLoS One 2014/Apr/15; 9(4): e94269. 13. Chowdhury MY, Li R, Kim JH, Park ME, Kim TH, Pathinayake P, Weeratunga P, Song MK, Son HY, Hong SP, Sung MH, Lee JS, Kim CJ. Mucosal vaccination with recombinant Lactobacillus casei-displayed CTA1-conjugated consensus matrix protein-2 (sM2) induces broad protection against divergent influenza subtypes in BALB/c mice. PLoS One 2014/Apr/08; 9(4): e94051. 14. Date KA, Bentsi-Enchill AD, Fox KK, Abeysinghe N, Mintz ED, Khan MI, Sahastrabuddhe S, Hyde TB. Typhoid Fever surveillance and vaccine use - South-East Asia and Western pacific regions, 2009-2013. MMWR Morb Mortal Wkly Rep 2014/Oct/03; 63(39): 855-60. 15. Desai SN, Cravioto A, Sur D, Kanungo S. Maximizing protection from use of oral cholera vaccines in developing country settings: An immunological review of oral cholera vaccines. Hum Vaccin Immunother 2014/May; 10(6): 1457-65. 16. Desai SN, Kamat D. Closing the global immunization gap: delivery of lifesaving vaccines through innovation and technology. Pediatr Rev 2014/Jul; 35(7): e32-40. 17. Dixit SM, Johura FT, Manandhar S, Sadique A, Rajbhandari RM, Mannan SB, Rashid MU, Islam S, Karmacharya D, Watanabe H, Sack RB, Cravioto A, Alam M. Cholera outbreaks (2012) in three districts of Nepal reveal clonal transmission of multi-drug resistant Vibrio cholerae O1. BMC Infect Dis 2014/Jul/15; 14: 392. 18. Firdous J, Islam MA, Park SM, Cheon IS, Shim BS, Yoon HS, Song M, Chang J, Choi YJ, Park YM, Boraschi D, Han SH, Cho CS, Yun CH. Induction of long-term immunity against respiratory syncytial virus glycoprotein by an osmotic polymeric nanocarrier. Acta Biomater 2014/ Nov; 10(11): 4606-17. 19. Hervouet C, Luci C, Bekri S, Juhel T, Bihl F, Braud VM, Czerkinsky C, Anjuere F. Antigen-bearing dendritic cells from the sublingual mucosa recirculate to distant systemic lymphoid organs to prime mucosal CD8 T cells. Mucosal Immunol 2014/Mar; 7(2): 280-91. 20. Kanungo S, Lopez AL, Ali M, Manna B, Kim DR, Mahapatra T, Holmgren J, Dhingra MS, Weirzba TF, Nair GB, Bhattacharya SK, Clemens JD, Sur D. Vibriocidal antibody responses to a bivalent killed whole-cell oral cholera vaccine in a phase III trial in Kolkata, India. PLoS One 2014/May/06; 9(5): e96499. 21. Kanungo S, Mahapatra T, Bhaduri B, Mahapatra S, Chakraborty ND, Manna B, Sur D. Diarrhoea-related knowledge and practice of physicians in urban slums of Kolkata, India. Epidemiol Infect 2014/Feb; 142(2): 314-26. 22. Kar SK, Pach A, Sah B, Kerketta AS, Patnaik B, Mogasale V, Kim YH, Rath SB, Shin S, Khuntia HK, Bhattachan A, Puri MK, Wierzba TF, Kaljee LM. Uptake during an oral cholera vaccine pilot demonstration program, Odisha, India. Hum Vaccin Immunother 2014/Oct/03; 10(10): 2834-42. 23. Kar SK, Sah B, Patnaik B, Kim YH, Kerketta AS, Shin S, Rath SB, Ali M, Mogasale V, Khuntia HK, Bhattachan A, You YA, Puri MK, Lopez AL, Maskery B, Nair GB, Clemens JD, Wierzba TF. Mass vaccination with a new, less expensive oral cholera vaccine using public health infrastructure in India: the odisha model. PLoS Negl Trop Dis 2014/Feb/06; 8(2): e2629. 24. Kim DR, Ali M, Thiem VD, Wierzba TF. Socio-ecological risk factors for prime-age adult death in two coastal areas of Vietnam. PLoS One 2014/Feb/26; 9(2): e89780. 25. Kim EH, Park HJ, Han GY, Song MK, Pereboev A, Hong JS, Chang J, Byun YH, Seong BL, Nguyen HH. Intranasal adenovirus-vectored vaccine for induction of long-lasting humoral immunity-mediated broad protection against influenza in mice. J Virol 2014/Sep/01; 88(17): 9693-703. 26. Kim EJ, Lee D, Moon SH, Lee CH, Kim SJ, Lee JH, Kim JO, Song M, Das B, Clemens JD, Pape JW, Nair GB, Kim DW. Molecular Insights Into the Evolutionary Pathway of Vibrio cholerae O1 Atypical El Tor Variants. PLoS Pathog 2014/Sep/18; 10(9): e1004384. 27. Kim H, Kim JK, Song H, Choi J, Shim B, Kang B, Moon H, Yeom M, Kim SH, Song D, Song M. Preliminary study about sublingual administration of bacteria-expressed pandemic H1N1 influenza vaccine in miniature pigs. J Microbiol 2014/ Sep; 52(9): 794-800. INTERNATIONAL VACCINE INSTITUTE 39 28. Kim JH, Nelson KE, Panzner U, Kasture Y, Labrique AB, Wierzba TF. A systematic review of the epidemiology of hepatitis E virus in Africa. BMC Infect Dis 2014/Jun/05; 14: 308. 29. Kim K, Jeong BG, Ki M, Park M, Park JK, Choi BY, Yoo WS. The costs of hepatitis A infections in South Korea. Epidemiol Health 2014/Aug/18; 36: e2014011. 30. Kim SA, Capeding MR, Kilgore PE. Factors influencing healthcare utilization among children with pneumonia in Muntinlupa City, the Philippines. Southeast Asian J Trop Med Public Health 2014/May; 45(3): 727-35. 31. Kothari N, Genschmer KR, Kothari S, Kim JA, Briles DE, Rhee DK, Carbis R. Preparation and testing of a Vi conjugate vaccine using pneumococcal surface protein A (PspA) from Streptococcus pneumoniae as the carrier protein. Vaccine 2014/Sep/29; 32(43): 5755-60. 32. Kothari S, Kim JA, Kothari N, Jones C, Choe WS, Carbis R. Purification of O-specific polysaccharide from lipopolysaccharide produced by Salmonella enterica serovar Paratyphi A. Vaccine 2014/ May/01; 32(21): 2457-62. 33. Kweon MN. Recent progress in mucosal immunology and vaccine development. Exp Mol Med 2014/Mar/14; 46: e86. 34. Kwon JS, Yoon J, Kim YJ, Kang K, Woo S, Jung DI, Song MK, Kim 40 ANNUAL REPORT 2014 EH, Kwon HI, Choi YK, Kim J, Lee J, Yoon Y, Shin EC, Youn JW. Vaccinia-based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection. Eur J Immunol 2014/Aug; 44(8): 2360-9. 35. Lim JK, Kim TH, Kilgore PE, Aiello AE, Choi BM, Lee KC, Yoo KH, Song YH, Kim YK. The association between influenza treatment and hospitalizationassociated outcomes among Korean children with laboratory-confirmed influenza. J Korean Med Sci 2014/Apr; 29(4): 485-93. 36. Mahmud J, Rashed SM, Islam T, Islam S, Watanabe H, Cravioto A, Alam M. Type three secretion system in non-toxigenic Vibrio cholerae O1, Mexico. J Med Microbiol 2014/Dec; 63(Pt 12): 1760-2. 37. Mathew MA, Paulose A, Chitralekha S, Nair MK, Kang G, Kilgore P. Prevalence of rotavirus diarrhea among hospitalized under-five children. Indian Pediatr 2014/Jan/08; 51(1): 27-31. 38. Mogasale V, Desai SN, Mogasale VV, Park JK, Ochiai RL, Wierzba TF. Case Fatality Rate and Length of Hospital Stay among Patients with Typhoid Intestinal Perforation in Developing Countries: A Systematic Literature Review. PLoS One 2014/Apr/17; 9(4): e93784. 39. Mogasale V, Maskery B, Ochiai RL, JS Lee, Mogasale VV, Ramani E, YE Kim, JK Park, Wierzba TF. Burden of typhoid fever in low-income and middle-income countries: a systematic, literature-based update with risk-factor adjustment. Lancet Glob Health 2014/Oct; 2(10): e570-80. 40. Nahar Q, Sultana F, Alam A, Islam JY, Rahman M, Khatun F, Alam N, Dasgupta SK, Marions L, Ashrafunnessa, Kamal M, Cravioto A, Reichenbach L. Genital human papillomavirus infection among women in Bangladesh: findings from a population-based survey. PLoS One 2014/Oct/01; 9(10): e107675. 41. Nelson CB, Mogasale V, Bari TI, Clemens JD. Considerations around the introduction of a cholera vaccine in Bangladesh. Vaccine 2014/Dec/12; 32(52): 7033-6. 42. Norrby R. Outlook for a dengue vaccine. Clin Microbiol Infect 2014/May; 20 Suppl 5: 92-4. 43. Ochiai RL, Khan MI, Soofi SB, Sur D, Kanungo S, You YA, Habib MA, Sahito SM, Manna B, Dutta S, Acosta CJ, Ali M, Bhattacharya SK, Bhutta ZA, Clemens JD. Immune responses to Vi capsular polysaccharide typhoid vaccine in children 2 to 16 years old in Karachi, Pakistan, and Kolkata, India. Clin Vaccine Immunol 2014/May; 21(5): 661-6. 44. Park JK, Lee DH, Cho CH, Yuk SS, To EO, Kwon JH, Noh JY, Kim BY, Choi SW, Shim BS, Song MK, Lee JB, Park SY, Choi IS, Song CS. Supplementation of oil-based inactivated H9N2 vaccine with M2e antigen enhances resistance against heterologous H9N2 avian influenza virus infection. Vet Microbiol 2014/Mar/14; 169(3-4): 211-7. 45. Park SE, Marks F. A conjugate vaccine against typhoid fever. Lancet Infect Dis 2014/Feb; 14(2): 90-1. 46. Park SJ, Kim EH, Pascua PN, Kwon HI, Lim GJ, Decano A, Kim SM, Song MK, Shin EC, Choi YK. Evaluation of heterosubtypic cross-protection against highly pathogenic H5N1 by active infection with human seasonal influenza A virus or trivalent inactivated vaccine immunization in ferret models. J Gen Virol 2014/Apr; 95(Pt 4): 793-8. destructive inflammation. Expert Rev Vaccines 2014/Mar; 13(3): 417-27. 50. Thiry G, Hombach J, Constenla D, Carvalho A, Durbin A. New chapter unfolding in the fight against dengue with an unwritten ending. Trans R Soc Trop Med Hyg 2014/Oct; 108(10): 597-8. 51. Thompson CN, Kama M, Acharya S, Bera U, Clemens J, Crump JA, Dawainavesi A, Dougan G, Edmunds WJ, Fox K, Jenkins K, Khan MI, Koroivueta J, Levine MM, Martin LB, Nilles E, Pitzer VE, Singh S, Raiwalu RV, Baker S, Mulholland K. Typhoid fever in Fiji: a reversible plague? Trop Med Int Health 2014/Oct; 19(10): 1284-92. 52. Tissera H, Amarasinghe A, De Silva AD, Kariyawasam P, Corbett KS, Katzelnick L, Tam C, Letson GW, Margolis HS, de Silva AM. Burden of dengue infection and disease in a pediatric cohort in urban Sri Lanka. Am J Trop Med Hyg 2014/Jul; 91(1): 132-7. 53. Unger CC, Salam SS, Sarker MS, Black R, Cravioto A, Arifeen SE. Treating diarrhoeal disease in children under five: the global picture. Arch Dis Child 2014/Mar; 99(3): 273-8. 54. Yang JS, Kang SS, Yun CH, Han SH. Evaluation of anticoagulants for serologic assays of cholera vaccination. Clin Vaccine Immunol 2014/Jun; 21(6): 854-8. 55. Yang JY, Lee SN, Chang SY, Ko HJ, Ryu S, Kweon MN. A Mouse Model of Shigellosis by Intraperitoneal Infection. J Infect Dis 2014/Jan/15; 209(2): 203-15. 56. [Book Chapter] Halstead SB. Pathogenic Exploitation of Fc Activity. Antibody Fc: Linking Adaptive and Innate Immunity. 2014;333-50. 57. [Book Chapter] Sahastrabuddhe S, Nelson CB, Ochiai RL. Typhoid Fever Vaccines. IAP Textbook of Vaccines 2014;304-22. 58. [Book Chapter] Victor Raul Gomez Roman, Joseph C. Murray, Louis M. Weiner. Antibody-Dependent Cellular Cytotoxicity (ADCC). Antibody Fc: Linking Adaptive and Innate Immunity. 2014;1-27. 47. Riewpaiboon A, Piatti M, Ley B, Deen J, Thriemer K, von Seidlein L, Salehjiddawi M, Busch CJ, Schmied WH, Ali SM, The Typhoid Economic Study Group (GiDeok Pak, Leon R. Ochiai, Mahesh K. Puri, Na Yoon Chang, Thomas F. Wierzba, John D. Clemens). Cost of illness due to typhoid Fever in pemba, zanzibar, East Africa. J Health Popul Nutr 2014/Sep; 32(3): 377-85. 48. Tang DC. A trail blazed through DNA vaccine, noninvasive vaccine, and innateadaptive immunity duo. Hum Vaccin Immunother 2014/Aug; 10(8): 2143-6. 49. Tang DC, Nguyen HH. The Yin-Yang arms of vaccines: disease-fighting power versus tissueINTERNATIONAL VACCINE INSTITUTE 41 2014 Financial Summary REVENUE Bill & Melinda Gates Foundation (BMGF) Government of the Republic of Korea Swedish International Development Cooperation Agency (Sida) Corporations / Individuals / Others Korean Government Laboratory Support Investments (Interest Income) Total Income EXPENSES Program Services Laboratory Support Management & General Communication & Advocacy Total Expense Foreign Exchange Gain (Loss) Net Surplus (Deficit) ASSETS Cash and Cash Equivalents Bank Deposits Other Current Assets Other Assets Total Assets LIABILITIES AND NET ASSETS Grant Funds-Deferred Support Other Current Liabilities Net Assets Total Liabilities and Net Assets 42 ANNUAL REPORT 2014 20142013 13,915,719 3,243,477 10,591,248 1,967,362 - 4,434,552 1,947,422 72,912 23,614,082 1,705,861 4,647,797 785,428 7,507 19,705,203 20142013 20,130,889 1,095,012 3,042,428 802,065 25,070,394 (778,585) (2,234,897) 15,838,109 1,529,379 2,959,935 897,756 21,225,180 (52,373) (1,572,350) 2014 SOURCES OF REVENUE 19% 9,576,112 26,597,341 1,031,647 772,608 37,977,708 2014 2013 23,604,226 909,256 4,892,493 29,405,975 29,632,085 1,277,424 7,068,199 37,977,708 24% 2014 2013 59% 54% 9% 14% 10% Bill & Melinda Gates Foundation (BMGF) Government of the Republic of Korea Swedish International Development Cooperation Agency (Sida) Corporations / Individuals / Others Korean Government Laboratory Support Investments (Interest Income) 2014 EXPENSE ALLOCATION 20142013 19,727,307 8,056,188 860,065 762,415 29,405,975 4% 8% 12% 5% 3% 4% 14% 2014 7% 80% Program Services Laboratory Support Management & General Communication & Advocacy 2013 75% State Parties and / or Signatories to IVI's Establishment Agreement INTERNATIONAL VACCINE INSTITUTE 43 Vaccines, Children, and a Better World IVI ANNUAL REPORT 2014 Copyright 2014 International Vaccine Institute. All Rights Reserved. SNU Research Park, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742 Korea TEL: 02-872-2801, FAX: 02-872-2803 Contact iviinfo@ivi.int for more information: www.ivi.int
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