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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Johnjoe McFadden of the University of Surrey in the United Kingdom will modify the BCG vaccine currently used against bovine and human tuberculosis, and develop a complementary diagnostic test that can distinguish between tuberculosis infection and vaccination. BCG is the only effective tuberculosis vaccine, however it interferes with diagnostic tests, preventing the distinction between infection and vaccination, which is important for control efforts in developing countries. They will identify genes in the BCG vaccine that can be removed without affecting its activity in cattle and determine which of those genes are potentially strongly immunogenic and therefore easy to detect. Selected genes will be used to develop a complementary diagnostic skin test that would not cross-react with the modified vaccine. Next steps would be developing and evaluating the vaccine and skin test in cattle and subsequently in humans.
Liam Morrison and Ivan Morrison of the Roslin Institute, University of Edinburgh in the United Kingdom will develop a new type of drug for treating diseases in animals and humans caused by African trypanosomes, which cause significant disease in sub-Saharan Africa. African trypanosomes evade the host immune system by varying their surface proteins, which can be recognized by conventional antibodies, precluding the development of an effective vaccine. They will exploit an unconventional antibody subtype discovered in cattle, which they hypothesize targets unvarying conserved epitopes on African trypanosomes, as a more effective treatment. They will identify specific antibody fragments that bind to trypanosomes and test whether they can eliminate the pathogen using animal models. Subsequent work will focus on identifying the target pathogen proteins of these unconventional antibodies with a view to developing a vaccine.
Agenor Mafra-Neto of ISCA Technologies, Inc. in the U.S. will test whether an artificial lactic acid treatment (called abate) can trick disease-transmitting insects such as mosquitoes into infecting animals rather than their preferred human hosts, thereby reducing infection rates. Malaria-causing parasites are carried by mosquitoes, which identify the human hosts that help them reproduce by detecting the high levels of lactic acid in human perspiration. Cattle are resistant to malaria and many other human diseases transmitted by insects, and are often treated with deworming medication, which has a toxic effect on mosquitoes and their parasites. They will develop a stable formula of abate and test its effect on altering host choice of several disease-transmitting insects to determine which is most effective.
Charles Long of the College of Veterinary Medicine and Biomedical Sciences in the U.S. will develop a strategy for generating single vaccines against diseases that infect both humans and animals (zoonotic) for use in both species that can be locally produced in goat milk. They will select two antigens from pathogens causing seven zoonotic diseases, including tuberculosis and trypanosomiasis, and incorporate them into vectors for producing the vaccines in lactating dairy goats. The ability of each vaccine to induce a protective immune response in combination with a variety of adjuvants will then be tested in goats. Vaccine-producing goats could be shipped to regions in need where local farmers and businesses would be trained to produce the milk and prepare the vaccines.
Danae Schulz and Erik Debler of Rockefeller University in the U.S. will test whether a drug that was originally developed to treat cancer and heart disease can also kill trypanosomes, which are parasites that cause African trypanosomiasis in humans and cattle. Repurposing a drug already approved for a different disease is highly cost-effective as expensive human safety trials are already complete. This particular drug is a bromodomain inhibitor that interferes with the structure of chromatin, and they have shown that it destroys trypanosomes grown in vitro. They will test whether the drug can cure trypanosome infections in mice, and determine how the drug and its derivatives interact with trypanosomes using binding and structural studies. Subsequent studies would test the drug in cattle and humans.
Marya Lieberman of the University of Notre Dame in the U.S. will produce an inexpensive paper card that can easily and quickly measure the quality of over 50 common drugs used to treat both humans and animals. Current estimates indicate that 10-30% of human drugs used in the developing world are not what they are labelled. However, buyers do not have the means to easily evaluate them. They will develop a small paper card that reveals a color pattern upon contact with a specific drug, such as an antibiotic, representing that drug's chemical composition. Results can be interpreted by eye or by sending a photo of the card via mobile phone for automated computer analysis. They will evaluate the card specificity and sensitivity, and field test it on 2,000 drugs collected from retail outlets in Kenya to compare efficacy with established methods.
Matthew Bonds of Harvard University in the U.S. will quantify the economic burden of disease using a combined metric to incorporate disease impact on both human and animal health. Current measures of economic burden consider humans and animals independently, yet they are both influenced by disease and by the health of each other. They will develop an integrated model combining epidemiology and economic growth to uncover links between disease impact and income in both human and livestock systems. Their model will be tested in the field using target human and wildlife populations in Madagascar to quantify the overall economic burden of disease.
John McGiven of the Animal Health Veterinary Laboratories Agency in the United Kingdom, along with David Bundle of the University of Alberta in Canada, will evaluate a glycoconjugate vaccine for brucellosis that is safe, stable, inexpensive, and efficacious. Complementary diagnostics will allow for the differentiation of vaccinated and infected subjects and assist in the control of this insidious zoonotic disease. They will test both the vaccine and the diagnostic in a standardized mouse model.
George Warimwe of the Jenner Institute at the University of Oxford in the United Kingdom will develop a vaccine to protect a variety of species, including humans, sheep and cattle, against Rift Valley fever, which can cause serious illness. Current vaccines that are in development have safety concerns for use in humans. They have developed a Rift Valley fever vaccine using a replication-deficient simian adenovirus as a safe vector that is easy and inexpensive to manufacture, and have tested its safety and immunogenicity in mice, and begun field-testing in sheep in Kenya. They will test safety and immunogenicity of the vaccine and the effect of an adjuvant in calves and goats, and compare this with the data from mice and sheep.
Peter Rabinowitz of the University of Washington in the U.S., along with colleagues at Washington State University and CDC Kenya, will test whether unhealthy gut microbes in livestock that co-reside with humans in smallholder households can negatively influence the gut microbes in the humans, and whether this can be exploited to improve human health. The microbial community (microbiota) living in the gut is important for childhood health, growth and development. They will analyze the gut microbiotas of healthy and unhealthy children and co-residing companion and domestic animals in selected households in western Kenya to determine whether they are related. If they are, they will reset the animal microbiota using established fecal transplant methods and determine whether there is a corresponding positive effect on the microbiotas of the rest of the household.