Building on success: IVI to open BSL 3 lab to spur avian flu research in 2006 ‘Institute faces critical moment in development, with many opportunities’ In the year 2006, the International Vaccine Institute will step up its efforts to counter the threat of avian influenza, while building on success in its research programs tackling “neglected diseases” afflicting the world’s poor. “Our desire to provide more help to the world’s poor requires that we continually expand the scope of our programs. We are now moving into research on vaccines against additional diseases of importance, including pandemic influenza,” said Dr. John Clemens, Director General of the IVI, in his New Year´s message. “This is a critical moment in IVI’s development, with many opportunities for us to continue to expand our work for the poor, but with a need for additional funds to support this work.” The threat of a potential influenza pandemic is now higher than ever, with the deadly H5N1 bird virus having spread from Southeast Asia to the Middle East, Europe and Africa, and to the Indian subcontinent. “The IVI will build upon the Pandemic Influenza Consortium, Korea (PICK) by conducting research to develop and improve H5N1 flu vaccines and to enhance surveillance for bird flu disease in humans in Asia” Dr. Clemens said. Last August, the IVI organized the PICK consortium of organizations in Korea to address the programmatic and research needs to protect Korea and other countries against this major threat. The consortium, with the IVI as the focal point, consists of government agencies (Korea Center for Disease Control and Prevention, and Korea National Institute of Health), universities (Seoul National, Yonsei, POSTECH, Chonnam National), and companies (Green Cross Corp., Celltrion). This year, with support from the Korean Ministry of Education and Human Resource Development, the IVI will upgrade and expand its biosafety level 3 laboratory at its headquarters in Seoul, to allow it to handle dangerous microbes, such as the H5N1 flu virus. The Institute has been striving to create a molecular virology laboratory, which is crucial in characterizing emerging viruses and in selecting candidate vaccine strains amid growing fears of a potential influenza pandemic. While taking on new diseases, the IVI plans to continue expanding the geographical scope of its research beyond the 21 countries of Asia, Africa and Latin America in which it currently has programs. As a special focus, the Institute aims to launch vaccine programs for North Korean children. “I believe that IVI’s experience and expertise on vaccines against childhood diseases could be of great assistance to the public health programs of North Korea and other developing countries,” said Dr. Clemens, an expert in vaccine evaluation who has devoted most of his career to research on vaccines for the poor. “Although the IVI is only eight years old, it is already a major player in global efforts to bring new vaccines to the world’s poorest people.” Translational research gains momentum For the past several years, the IVI has been successfully spearheading global efforts to accelerate the development and introduction of new vaccines against diseases of the poor, including diarrheal diseases such as cholera, shigellosis, typhoid fever and rotavirus. IVI’s study of a licensed oral cholera vaccine in Mozambique has demonstrated for the first time that a vaccine can protect people in an area of Africa with a high level of HIV. The results of this study were published in the prestigious medical journal, The New England Journal of Medicine. The study prompted the Korean government to donate $500,000 to the IVI for the purchase of oral cholera vaccine to create a stockpile to help victims of a major, international natural disaster in the future. In addition, IVI’s evaluation of the long-term impact of a licensed oral cholera vaccine in Bangladesh demonstrated that a vaccine against cholera can protect against this disease through the combination of direct and herd immunity. The study was published in the leading medical journal, The Lancet. IVI scientists also conducted clinical studies of a newer generation, genetically-engineered oral vaccine against cholera, called “Peru 15,” in Bangladesh. The studies found this vaccine may offer improved protection over existing licensed vaccines. The Institute has successfully conducted effectiveness trials of a licensed typhoid vaccine in five Asian countries. This vaccine, Vi polysaccharide (PS), could prove highly effective in saving lives in developing countries. The trials immunized about 250,000 persons in the five sites, and surveillance for typhoid fever will be maintained in each site for two years following immunization. The trials are expected to provide information that will be critical for the introduction of this vaccine into health programs for the poor in typhoid-endemic areas. At the same time, the IVI has continued its research programs on other illnesses, including bacterial meningitis and pneumonia, and the mosquito-borne diseases, Japanese encephalitis (JE) and dengue fever. IVI’s studies in Vietnam conducted in 2005 demonstrated that a JE vaccine produced by a local manufacturer as well as a Korean vaccine (produced by Green Cross Corp), had a major effect in reducing incidence of this devastating disease in Vietnamese children. The Pediatric Dengue Vaccine Initiative (PDVI), a Gates Foundation-supported program aimed at accelerating the development and introduction of new vaccines against dengue, has launched studies in 13 countries of Asia and Latin America. PDVI´s activities fall into two major programs; (1) the Dengue Vaccine Evaluation Program, involving pre-clinical studies such as vaccine safety and dengue diagnostic activities, as well as field evaluation; and (2) the Vaccine Utilization Case Program, which involves studies of disease burden, cost of illness, comparative economics, and vaccine access at the country level. In all, the IVI is working on vaccines against diseases that collectively claim the lives of more than 5 million people worldwide each year. Innovative research in laboratory science On the laboratory science front, IVI scientists this past year improved the technology for the production of an effective oral cholera vaccine that is currently used in Vietnam. The improved vaccine is being transferred to India and Indonesia and will be tested in a field trial in 100,000 persons in Kolkata, India, beginning later this year, as a first step towards the wider use of this vaccine in India and elsewhere. In collaboration with the US National Institute of Health (NIH), the Institute is successfully developing a new Vi-protein conjugate typhoid vaccine in its laboratories in Seoul. “This new vaccine offers the promise of an even better vaccine than those currently available, and one that could be administered to children under two years of age and could provide long term protection,” Dr. Clemens noted. The IVI has also initiated development of new candidate Shigella vaccines that can be easily produced by local manufacturers and affordable to developing country populations. Studies are currently being conducted that will lead to the production of clinical lots of Shigella ribosomal vaccines in its laboratories. All equipment and analytics for this vaccine candidate will be accessible and affordable for emerging vaccine producers, and, if the vaccine proves successful, it could potentially be produced for pennies per dose in developing countries. “It has been only two years since IVI’s lab science became operational, but we have already seen significant synergistic effects between our translational research to speed up the introduction of vaccines and laboratory sciences to develop new vaccines,” said Dr. Clemens. “The opening of a BSL 3 lab will allow us to further expand our research to emerging viral pathogens.” The IVI will also continue to help countries expand their capacity in vaccine development and production, which will, for example, be instrumental to counter the threat of an influenza pandemic. As part of these efforts, the IVI will host its sixth annual “International Advanced Course on Vaccinology for the Asia-Pacific Regions” at its headquarters in May (see next article). The Institute will also conduct a course for the Developing Country Vaccine Manufacturers Network on modern approaches to vaccine trials. The IVI serves as a member of the WHO Global Training Network for Vaccine Production and Regulation. “If the IVI is to make the most of these many opportunities and continue to grow, however, further support of the Institute by donors will be instrumental,” said Dr. Clemens. He urges more philanthropists to join the IVI’s humanitarian efforts to protect the world’s poorest children with lifesaving vaccines.