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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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Challenges: Antigen Design
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A Protective Genetically Attenuated P. Falciparum Sporozoite Vaccine

Stefan Kappe, Seattle Biomedical Research Institute (Seattle, Washington, United States)
Jul 1, 2005

Attenuated vaccines, composed of weakened organisms incapable of causing disease, provide prolonged exposure to antigens and have proven effective against several viral or bacterial diseases. Dr. Kappe's team is attempting to extend this concept to a malaria vaccine. In the case of malaria, disease develops when the malaria sporozoite – the form of the parasite that is transmitted from mosquitoes to humans – enters the bloodstream and moves to the liver. There, it grows and divides into thousands of parasites that invade and destroy red blood cells, causing disease. Dr. Kappe's team is working toward development of a malaria vaccine using a malaria sporozoite that has been weakened by gene deletion to stimulate immune response. Kappe (Grand Challenges in Global Health: 2005-2015 retrospective)

Enhancing the Immunogenicity and Efficacy of Vectored Vaccines

Adrian Hill, University of Oxford (Oxford, United Kingdom)
Jul 1, 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)

Improved Vaccine Efficacy via Dendridic Cells and Flavivirus Vectors

Ralph Steinman, Rockefeller University (New York, New York, United States)
Jul 1, 2005

Dr. Steinman's team is developing vaccines that stimulate the immune system's dendritic cells, which are known to play an important role in stimulating protection against infectious diseases. One approach is to engineer vaccine antigens into monoclonal antibodies against receptors on the surface of dendritic cells. A secondary approach involves engineering genes for the antigens of interest into the yellow fever virus. The project will focus on creating experimental vaccines for a range of diseases, including HIV and malaria. If successful, this technology could identify a better way to create vaccines that stimulate multiple components of the body's immune response, including those that have been difficult to target with existing vaccine approaches.

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

Robin Shattock, St. George's Hospital Medical School (London, United Kingdom)
Jul 1, 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.

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View the Grand Challenges partnership network

The Bill & Melinda Gates Foundation is part of the Grand Challenges partnership network. Visit www.grandchallenges.org to view the map of awarded grants across this network and grant opportunities from partners.