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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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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)

Homing Endonuclease Genes: New Tools for Mosquito Population Engineering and Control

Austin BurtImperial College LondonLondon, United Kingdom
Grand Challenges in Global Health
Biological Vector Control
1 Jul 2005

The inability to ensure that newly introduced genes will become established within regional mosquito populations has been a major roadblock to the advancement of genetic strategies for vector control. Dr. Burt and his colleagues are investigating homing endonuclease genes (HEGs), so-called "parasitic" genes that can spread rapidly through mosquito populations even if they harm the host insect. This gives HEGs the potential to move newly introduced traits, such as sterility or inability to transmit disease, through a population quickly. The project's ultimate goal is to develop HEGs as a flexible, robust, powerful, and safe system to drive useful traits through populations of mosquitoes that transmit malaria. Burt (Grand Challenges in Global Health: 2005-2015 retrospective)

Drugs for Treatment of Latent Tuberculosis Infection

Douglas YoungImperial College LondonLondon, United Kingdom
Grand Challenges in Global Health
Curing Latent Infection
1 Jul 2005

An estimated 2 billion individuals - a third of the world's population - have been exposed to Mycobacterium tuberculosis (MTB) and carry the infection in its latent form, retaining a lifelong risk of developing TB disease. Programs to control tuberculosis now focus on childhood vaccination and treatment for people with active disease. Reversing TB's spread, however, requires an intervention that will prevent disease in those who are already infected. The lack of knowledge about the biology of latent TB infection stands in the way of the development of such an intervention. Dr. Young is leading an international team of researchers from the U.K., U.S., Singapore, Korea, and Mexico that is attempting to further elucidate the fundamental biology of latency and use this knowledge to develop drugs against latent TB. Young (Grand Challenges in Global Health: 2005-2015 retrospective)

A Live Recombinant Attenuated Salmonella Anti-Pneumococcal Vaccine for Newborns

Roy CurtissArizona State UniversityTempe, Arizona, United States
Grand Challenges in Global Health
Single-Dose Vaccines
1 Jul 2005

The current vaccine against bacterial pneumonia (pneumococcus) requires a regimen of four injections given at specific intervals. In developing countries, this not only complicates the vaccination process for health workers and children, but it also is a serious obstacle for families who must travel long distances to the nearest health clinic. Dr. Curtiss and his colleagues are working to develop new vaccines against bacterial pneumonia that require only a single dose, can be delivered orally, and are safe for newborns, infants, and people who are malnourished or whose immune systems are compromised.

Bacterial Spores as Vaccine Delivery Systems

Abraham SonensheinTufts University School of MedicineMedford, Massachusetts, United States
Grand Challenges in Global Health
Vaccines Without Refrigeration
1 Jul 2005

To maintain stability and viability, most childhood vaccines must be kept cool - both heat and freezing can ruin them. That means they must be refrigerated at the correct temperature throughout transportation, storage, and delivery. This cold chain is difficult and costly to maintain, especially in developing countries. Dr. Sonenshein and his team are working to create childhood vaccines for diphtheria, tetanus, and pertussis (the DTP combination vaccine), and rotavirus-related diarrhea that can withstand a wide range of temperatures without refrigeration by encapsulating them in harmless bacterial spores that are naturally heat-resistant.

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