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Grand Challenges is a family of initiatives fostering innovation to solve key global health and development problems. Each initiative is an experiment in the use of challenges to focus innovation on making an impact. Individual challenges address some of the same problems, but from differing perspectives.

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Natural Products Inhibit Intracellular Microorganisms via Cellular Mechanisms

Jian-Dong JiangInstitute of Medicinal Biotechnology, Chinese Academy of Medical SciencesBeijing, China
Grand Challenges in Global Health
Drug Resistance
1 Jul 2005

Dr. Jiang’s team is identifying components of human cells that microbes use to establish an infection and replicate but that are not essential to the human host. Better understanding of microbial replication and survival from the view of host cells, the project team anticipates, will provide a foundation for novel therapeutic approaches to combat infectious diseases while simultaneously providing a low likelihood of inducing drug resistance. These compounds could potentially work by interrupting microbes from creating the environment they need to replicate in human cells.

Preclinical and Clinical Evaluation of Post-Exposure TB Vaccine

Peter AndersenStatens Serum InstitutCopenhagen, Denmark
Grand Challenges in Global Health
Curing Chronic Infection
1 Jul 2005

To stop the spread of tuberculosis, scientists are working to develop methods that prevent new infections and also eliminate infection in the huge reservoir of people who already are infected with MTB. New approaches that focus on controlling or stimulating the immune system to cure latent infections or prevent MTB from causing disease have the potential to significantly reduce illness, death, and disease transmission. Dr. Andersen’s is leading a collaborative team of international researchers who are studying Mycobacterium tuberculosis to identify the mechanisms that, in some people, allow it to escape natural immune system responses. The project's ultimate goal is to develop vaccines that target latent TB, either before or after an individual is infected.

Immunity to Prevent Pneumococcal Transmission: Correlates of Protection and Herd Immunity

Helena KäyhtyNational Institute for Health and WelfareHelsinki, Finland
Grand Challenges in Global Health
Protective Immunity
1 Jul 2005

Acute respiratory infections, often due to Streptococcus pneumoniae (pneumococcus), are a primary cause of death in young children in developing countries. A new vaccine effectively prevents the most serious form of pneumococcal disease and also reduces nasopharyngeal colonization with pneumococci. Because only some people who are infected become ill, researchers must study tens of thousands of vaccinated individuals over a long period of time to determine whether the vaccine guards against disease. Dr. Käyhty is leading an international consortium of investigators whose goal is to establish a quick and inexpensive method of determining the efficacy and expected effectiveness of the pneumonia vaccine.

Novel Mouse Models for Testing HIV and HCV Vaccines

Rudi BallingThe Helmholtz Centre for Infection ResearchBraunschweig, Germany
Grand Challenges in Global Health
Vaccine Model Systems
1 Jul 2005

Hepatitis C virus (HCV) is a major cause of liver diseases, including cirrhosis and liver cancer. Treatment for chronic hepatitis C is often out of financial reach for people in developing countries, and there is no vaccine against the virus. To prepare a human vaccine, investigators need an animal model that can help them screen and prioritize vaccine candidates. Dr. Balling's team, partnering with Dr. Di Santo's group at the Institut Pasteur in France, is working toward the development of mice with livers and immune systems that are similar to those of humans. These animals might be used to test vaccines for HCV, and potentially, other human pathogens.

Biomarkers of Protective Immunity and Surrogate Markers of TB Disease in Africa

Stefan KaufmannMax Planck Society for the Advancement of Science EVBerlin, Germany
Grand Challenges in Global Health
Protective Immunity
1 Jul 2005

Tuberculosis (TB) is a major health problem, especially in developing countries. Dr. Kaufmann is leading an international consortium that is studying differences in immune system responses between people exposed to TB who never become sick and those who develop the disease, focusing particular attention on people infected with both HIV and TB in endemic African countries. The project's participating laboratories in Europe and the United States are attempting to learn which host responses provide protective immunity against TB and to identify correlates of protective immunity and host biomarkers of TB disease that could help guide the design and testing of improved TB vaccines, drugs, and diagnostics.

Engineering Rice for High Beta-Carotene, Vitamin E and Enhanced Fe and Zn Bioavailability

Peter BeyerAlbert Ludwigs Universitat FreiburgFreiburg, Germany
Grand Challenges in Global Health
Crop Biofortification
1 Jul 2005

Although rice is a primary source of food for much of the world's population, it is a poor source of many essential micronutrients, as well as protein. As a result, widespread reliance on rice is the primary cause of micronutrient malnutrition throughout much of the developing world. Dr. Beyer is leading an international, collaborative effort called the ProVitaMinRice Consortium. The consortium's members are developing new varieties of rice with increased levels or bioavailability of pro-vitamin A, vitamin E, iron, and zinc as well improved protein quality and content. As their platform, the consortium's researchers are using Golden Rice, which has been genetically engineered to produce and accumulate pro-vitamin A in the grain, and are working with novel transgene-based technologies to enhance the availability of the target nutrients.

Surface Modified Nanostructures as Delivery Vehicles for Transmucosal Vaccination

Maria AlonsoUniversity of Santiago de CompostelaSantiago de Compostela, Spain
Grand Challenges in Global Health
Needle-Free Vaccines
1 Jul 2005

Most vaccines are delivered by injection, which increases the risk that HIV, hepatitis, and other serious diseases may be transmitted by syringes and needles that are not sterile. Dr. Alonso's team is working to develop a new generation of delivery systems that can easily and effectively carry hepatitis B vaccine through the mucosal lining of the nose. In addition, the team is evaluating whether these delivery systems and the vaccine they carry can be freeze-dried into an inhaled powder that could be stored without refrigeration.

Enhancing the Immunogenicity and Efficacy of Vectored Vaccines

Adrian HillUniversity of OxfordOxford, United Kingdom
Grand Challenges in Global Health
Antigen Design
1 Jul 2005

Dr. Hill and his colleagues are exploring a novel approach to enhancing the ability of plasmid DNA, pox, or adenoviral vectored vaccines to stimulate strong immune responses. Building on recent advances in understanding of pattern recognition molecules as well as intracellular signaling pathways, investigators are working to add intracellular adjuvants (molecular signals that have the potential to enhance immunogenicity) to the vaccine vectors. Also being explored is the effect of adding molecules designed to inhibit regulatory pathways that may be limiting protective immune response. The team is focusing on improving vectors for vaccines against malaria, HIV, and tuberculosis. Hill (Grand Challenges in Global Health: 2005-2015 retrospective)

Novel Antigen Design and Delivery for Mucosal Protection Against HIV-1 Infection

Robin ShattockSt. George's Hospital Medical SchoolLondon, United Kingdom
Grand Challenges in Global Health
Antigen Design
1 Jul 2005

Dr. Shattock and collaborators in the U.K. and South Africa will attempt to develop an HIV vaccine that stimulates immunity to the virus in the lining of the vagina. The investigators hypothesize that an HIV vaccine will be most effective at the site where the virus enters the body. Innovative combinations of vaccine antigen formulas and delivery technologies will be used to develop a potentially potent and effective vaccine. The vaccine will be designed to be delivered via low-cost vaginal gels or via silicone rings that fit inside the vagina and can be self-administered.

Learning from the Human Genome How Protective Immunity Against Malaria Works

Dominic KwiatkowskiUniversity of OxfordOxford, United Kingdom
Grand Challenges in Global Health
Protective Immunity
1 Jul 2005

Due to differences in their immune systems, individuals respond to malaria in different ways. While some die, others survive, and still others are infected without becoming ill. Understanding how and why some people naturally resist malaria may help lead to the development of an effective vaccine against the disease. Dr. Kwiatkowski is leading the Malaria Genomic Epidemiology Network, or MalariaGEN, an international partnership of malaria research groups. MalariaGEN partners in 20 countries, including in 14 countries where malaria is endemic, are combining genomic technology with large-scale epidemiological analyses to identify mechanisms of protective immunity against malaria in humans. Their ultimate goal is to guide the development of tools and markers to facilitate the design and testing of vaccines against malaria. Kwiatkowski (Grand Challenges in Global Health: 2005-2015 retrospective)

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