Jack McPartland of Future Buro in Australia will work to turn the figure "0.7%" – which is the United Nations target for aid donations from the Gross Domestic Product (GDP) of developed countries – into a brand that can be communicated to tell the story about the proportionally small amount of financial resources needed to make an impact in the developing world. After branding is created, Future Buro will work to secure partnerships to facilitate donations of 0.7% of incomes, budgets, and media space to expand the reach of targeted communications about the positive impact of foreign aid.

Juliana Cassataro of the Universidad Nacional de San Martín-CONICET in Argentina will test whether the bacterial protease inhibitor Omp19 can make vaccines more effective when they are administered orally. Oral delivery of vaccines is far simpler than by injection, which is particularly useful in low-resource settings, and it may also stimulate mucosal immunity making them more effective against some diseases. However, most vaccines administered orally are degraded in the stomach or do not induce a sufficient immune response to protect against the disease. In Phase I, while at the Universidad de Buenos Aires-CONICET, they discovered that Omp19 protects antigens from degradation and serves as an adjuvant, contributing to induction of both a mucosal and systemic immune response in mice orally immunized with proteins from the Salmonella bacterium and the Toxoplasma parasite, both of which have mucosal routes of infection. In Phase II, they will extend their mechanistic studies in order to move towards a Phase I clinical trial, and evaluate the ability of Omp19 to help induce an immune response in mice upon oral vaccination against Enterotoxigenic E. coli (ETEC), which is the most common cause of bacterial diarrhea in children from developing countries.

Ben Gilbert and Andrew Brown of the University of Canberra in Australia will develop a regional support network for medical supply managers in Pacific Island countries that can help them to better apply the formal training they received to manage vaccine supply systems. By engaging them in a buddy support system, Gilbert and Brown hope to empower these managers to overcome cultural, educational, social and historical factors that hinder effective management styles, and help them operate supply systems that are more responsive to immunization challenges in those developing countries.

Christopher Vinnard of Drexel University in the U.S. proposes to develop a low-cost point-of-care urine test that can safely and accurately identify tuberculosis patients who poorly absorb anti-TB drugs. Testing patients for inadequate drug bioavailability could enable better drug dose optimization and decrease transmission rates.

Koen Dechering of TropIQ Health Sciences in the Netherlands is developing a high-throughput functional assay to identify new compounds that specifically block transmission of the malaria parasites to their vector hosts, which is a difficult stage to target, and to test candidate drugs. The assay incorporates luciferase- expressing parasites, which emit light as they develop in the mosquito midgut, along with barcoded chemical libraries. In Phase I, they tested several barcoding strategies and identified a bacterium that could be genetically modified to carry a unique barcode for identifying hit compounds selected in the screen. They also developed the luminescent reporter parasite to track transmission. In Phase II, they will further develop the assay for higher throughput, and screen compounds from the Tres Cantos Antimalarial Set and the MMV Validation, Malaria and Pathogen boxes. They will also use the assay to characterize the mechanisms of action of other candidate transmission-blocking compounds.

Alice Telesnitsky of the University of Michigan in the U.S. seeks to define and characterize HIV interactions with host RNA. The team will attempt to determine whether disrupting or mimicking essential interactions with host RNAs may lead to antiviral strategies to which HIV cannot readily develop resistance.

Ahsan Khandoker of Khalifa University in the United Arab Emirates will build a low-cost, non-invasive abdominal phonogram device that can be used on a mobile phone to assess sounds that indicate fetal well being such as heart rate and body movement. The device will employ a software algorithm to extract fetal noises in an acoustic signal from maternal and environmental noises, allowing health care workers in remote locations to conduct obstetric assessments without expensive or invasive equipment.

Christina Smolke of Stanford University in the U.S. will develop synthetic biology platforms to improve the scale and efficiency of microbial systems used to discover, develop, and produce drugs based on natural products. Such new biosynthesis approaches could lead to new and less expensive drugs for global health.

Alain Labrique of Johns Hopkins Bloomberg School of Public Health in the U.S. will develop and field test in rural Bangladesh a cloud-based mobile phone system that will allow for universal access to vaccination records, send vaccine reminders and messaging, and provide incentives to parents and health care workers via a phone application. This new strategy could increase the reach, coverage, and public acceptance of immunization.

Daniel Stein and Phillip DeShong of the University of Maryland in the U.S. will construct and test a vaccine platform that utilizes low-cost, stable surfactant vesicles to deliver antigens for a sustained mucosal immune response. If successful, the platform could be used to develop low-cost vaccines for bacterial infections where carbohydrates form the basis of protective immunity, such as bacterial pneumonia and diarrheal diseases.

Philip J. Shaw of Thailand's National Center for Genetic Engineering and Biotechnology will seek to identify potential drug targets and vaccine antigens in the malaria parasite using a novel technology to reduce specific gene expression. By fusing a natural genetic “riboswitch” onto gene targets, the team will attempt to attenuate gene expression and thereby determine gene function.

Miguel Prudencio of Instituto de Medicina Molecular in Portugal will test the theory that modified live rodent malaria parasites (P. berghei) can be used in a vaccine to elicit a strong immune response in humans without being able to infect human red blood cells and cause illness. This was successfully tested in Phase I, and they also established that the human antigens carried by the parasites could induce a selective immune response in mice. In Phase II, they will test their vaccine in Phase I/IIa human trials and evaluate it for safety, tolerability, and immunogenicity. They will also extend their approach to another human malaria parasite P. vivax, and begin optimizing methods for large-scale vaccine production.

Kuan-Teh Jeang of the National Institutes of Health in the U.S. will investigate whether cells infected by one virus become resistant to infection from other viruses, and if this viral interference can confer protection against HIV. The team will develop an attenuated virus to test whether over-expression of viral envelope proteins within cells can confer resistance to further HIV infection.

Anders Hakansson of the University of Buffalo in the U.S. has identified a protein from human breast milk (Human Alpha Lactalbumin Made Lethal to Tumor cell, or HAMLET), that kills respiratory tract bacteria. Hakansson will attempt to understand the mechanism by which HAMLET binds to and kills pheumococci without the bacteria developing resistance.

Renjie Chang of Lavax in the U.S. will develop and test a vaginal suppository that uses a strain of commensal bacteria which has the ability to immobilize sperm and capture viruses. If successful, the bacteria could be used as a reversible contraceptive that also affords protection against viruses such as HIV and herpes.

Giulietta Saletti of the International Vaccine Institute in the Republic of Korea will work to develop an assay test that binds to tissue-specific cell markers to not only measure the concentration of anti-body secreting cells, but also identify which of those cells are targeted to mucosal tissues. If successful, this simple test that requires a small blood sample can be used in low-resource settings to measure mucosal immune responses to vaccines in infants and children.

Paul Gilson of Macfarlane Burnet Institute for Medical Research and Public Health in Australia will study the function of a newly discovered malaria parasite mechanism that exports proteins into host red blood cells in an effort to develop compounds that block this transfer and inhibit parasite growth.

To optimize the effectiveness of current anti-tuberculosis drugs, Boitumelo Semete of the CSIR in South Africa will work with collaborators to develop “sticky nanoparticles” that specifically attach to TB-infected cells. Once taken in by these cells, the nanoparticles will slowly degrade, releasing the anti-TB drugs and killing the bacteria. With this novel drug delivery system, the team aims to improve the bioavailability of the current therapies, with the possibility of shortening the treatment period for TB as well as reduce drug side effects.

Alexander Douglas of the Jenner Institute, University of Oxford in the United Kingdom will use synthetic nucleic acid molecules known as aptamers to develop a model that can be used to predict the success or failure of new vaccines in clinical trials. This work could help to remove some of the uncertainty in the early-stage development of new vaccines.

David Sullivan of the Johns Hopkins Bloomberg School of Public Health in the U.S., along with Martin N. Martinov of Gradient Biomodeling LLC, will create a quantum physics computer model of liver-stage malaria parasite infection to screen existing commercial drug and compound databases to identify molecules that possess liver-stage specific anti-malarial activity. Those molecules will then be tested in vivo and in vitro, and the ones that are effective will be optimized via computer modeling for future pre-clinical development.

Enterotoxigenic E. coli (ETEC) is the leading cause of diarrhea in the developing world. Roy Robins-Browne, of the University of Melbourne, in Australia will evaluate the effectiveness of a prototype vaccine that combines enterotoxin of E. coli (which lacks immunogenicity by itself) with another epitope to attract helper T cells and a lipid adjuvant to ensure delivery of the antigen directly into the cell.

Stéphane Blanc of the Institut National de la Recherche Agronomique (INRA) in France will minimize the destructive effects of aphids on crop plants by studying a newly described structure, the acrostyle, which is found at the tip of the piercing mouthparts of the insects and thought to be important for feeding and for transmitting disease-causing viruses between plants. Aphids spread an array of different plant viruses to many crop species including banana, chickpea, and sweet potato. Work during Phase I involved developing tools including acrostyle-targeting antibodies and methods to genetically manipulate aphids, which led to the identification of one protein in the acrostyle that is likely to be a receptor for the cauliflower mosaic virus. Consistent with this, binding of this virus to the insect could be blocked with an antibody targeting that specific protein. In Phase II, they will complete their cataloguing of peptides at the acrostyle using mass spectrometry to identify more candidate receptors that are important for virus binding and transmission, and potentially also for insect feeding. These peptides will be further analyzed using newly developed genetic tools to determine their precise function. They will also use structural methods including nuclear magnetic resonance to identify key amino acid residues in the peptides that could be exploited to block both virus transmission and insect feeding, and thereby weaken the aphids.

Kevin Plaxco of the University of California, Santa Barbara, United States seeks to develop a diagnostics platform based upon measuring the electric current produced by the binding of antibodies to DNA molecules. If successful, this method will provide a rapid, single-step reagent free measurement of immune antibodies which could significantly augment disease detection and vaccine validation efforts.

Amitava Mitra of the University of Nebraska in the U.S. will investigate direct repeat- induced gene silencing, a phenomenon of RNA interference in which genes adjacent to a target gene are also silenced. This "transitive silencing" will be tested for its ability to target multiple crop viruses at once, allowing the development of a transgenic wheat strain that is resistant to multiple major diseases.

Antibodies and the complement system work together to specifically detect and clear viruses, but they are circumvented by HIV, which hides itself and the cells it infects by hijacking host proteins such as CD59. Qigui Yu of Indiana University School of Medicine in U.S. will attempt to unmask HIV and HIV-infected cells and render them susceptible to antibody-complement attack. In this project's Phase I research, Yu and his team identified a potent, specific, and non-toxic inhibitor of human CD59, which is used by HIV to escape destruction by antibody-complement attack. In Phase II, Yu will continue to research how this inhibitor might allow antibodies to regain their complement-mediated activity to destroy the virus and HIV-infected cells, and will also research how HIV-1 incorporates human CD59 onto viral particles to escape antibody-complement immunity.

Melvin Reichman of the LIMR Chemical Genomics Center Inc. in the U.S., working with Vicky Avery of the Eskitis Institute for Cell and Molecular Therapies in Australia, will develop and validate a new drug screening approach called Ultra-High Throughput Screening for Synergy (uHTSS) to discover new drug combinations from the Tres Cantos anti-malarial set for the treatment of malaria.

Anton Middelberg of the University of Queensland in Australia proposes to develop a new vaccine for rotavirus by the directed self-assembly of a safe virus-like particle in industrial reactors. The approach uses low-technology engineering methods suitable for the developing world, ensuring relevance to the communities most in need of vaccine.

Sumi Biswas of the Jenner Institute, University of Oxford in the United Kingdom will test three components from the mosquito's innate signaling pathways for possible use in a malaria vaccine. Biswas will test whether immunizing mammal hosts with these components can induce strong antibodies, which can be passed along to mosquitoes to enhance the insect's innate immune response, thus leading to the death of the malaria parasite in the vector.

Bryce Chackerian and David Peabody at the University of New Mexico in the U.S. have developed a new phage display system based on highly immunogenic virus- like particles (VLPs), and will utilize this new system as a platform to identify new vaccines that induce broadly neutralizing antibodies against HIV.

James Beeson and Damien Drew of the Burnet Institute in Australia propose to generate chimeric Plasmodium falciparum that expresses the antigens of another malaria parasite, P. vivax, allowing them to be evaluated as vaccine candidates. Because laboratory culturing of P. vivax is costly and technically difficult, this new method could help accelerate the development of vaccines against malaria caused by P. vivax.

Frans Walther of the Los Angeles Biomedical Research Institute in the U.S. will adapt a low-cost synthetic lung surfactant for aerosol delivery as a non-invasive and simple method to support breathing in premature infants. Surfactant is composed of lipids and proteins, and keeps the lungs open during expiration. It is normally administered to premature infants with breathing difficulties by tracheal intubation, which can be problematic in low-resource settings and cause side effects. In Phase I, they produced the surfactant aerosol and found that it improved oxygenation and lung function in a small animal model. In Phase II, they will continue preclinical development by analyzing different application methods, dosing levels, and safety, and evaluate dry surfactant formulations that would not require refrigeration.

Jason Rasgon of the Johns Hopkins Bloomberg School of Public Health in the U.S. will engineer a virus to express a scorpion toxin that kills mosquitoes. After infecting mosquito larvae, the virus will express the killer gene when the insect becomes old enough to reproduce, but not old enough to transmit the malaria parasite. By allowing the mosquito to reproduce, the virus not only will be transmitted vertically to the next generation, but will also significantly slow the evolution of resistance to the gene.

Mosquito transmitted pathogens such as dengue and malaria are a significant disease burden on the world's population. Paul Young of the University of Queensland in Australia aims to develop a novel vaccine approach that is based on blocking mosquito transmission of these disease agents rather than inducing pathogen- specific immunity.

Michael Leibowitz of the UMDNJ-Robert Wood Johnson Medical School in the U.S. will investigate whether malaria parasites bind to, invade and replicate in the endothelial cells that line the blood vessels to test the theory that endothelial cells play an important role in the development of malaria infection and may serve as undiscovered reservoirs for parasite latency.

Gérrard Poinern of Murdoch University in Australia will develop and test an implantable subcutaneous device made from same calcium mineral that bones are made of, which will release contraceptive drugs in a sustained and controlled way for a period of months. Creating of this device uses ultrasound and microwave technology, allowing for eventual low-cost manufacture in developing countries.

Michael Klemba of Virginia Polytechnic Institute and State University in the U.S. will identify anti-malarial compounds from the Malaria Box that function as inhibitors of the cytostomal endocytic pathway used by the malaria parasite P. falciparum to internalize host erythrocyte proteins. Characterizing the molecular mechanisms of this process could lead to the discovery of new anti-malarial compounds.

Gerald R. Smith of the Fred Hutchinson Cancer Research Center in the U.S. seeks to identify inhibitors of a bacterial DNA repair enzyme that allows tuberculosis to mutate. Identifying these inhibitors could lead to therapies that kill bacteria and limit drug resistance.

Lena Hulden of the University of Helsinki in Finland will test the hypothesis that saliva from newly emerging mosquitoes activates dormant P. vivax parasites in the liver. By robust statistical analysis of the timing of P. vivax outbreaks, as well as molecular analysis of mosquito saliva, Hulden hopes to eventually identify the trigger for these relapses in hopes of controlling outbreaks.

Ruth Stringer and a team at Health Care Without Harm in the U.S., and colleagues at the Health Care Foundation Nepal, will design and test a decision-making tool that compares the costs, benefits, and environmental impacts of centralized autoclaving, recycling, and/or disposing of various types of conventional and safety syringes. This tool will enable decision makers to choose the most economical and sustainable medical waste management strategy.

David Mabey of the London School of Hygiene and Tropical Medicine in the United Kingdom and his team will test whether treatment with the broad­-spectrum antibiotic azithromycin can prevent growth faltering linked to environmental enteropathy, which is prevalent in young children of developing countries. They will utilize a double blind, randomized, controlled trial of Malawian children aged 1­-60 months, and analyze growth over a two year period after a single administration of either the antibiotic or a placebo control. They will also analyze immune responses and composition of the intestinal microbiota to identify the molecular pathways underlying environmental enteropathy. Their aim is to improve growth and development in affected infants in low­-income countries.

Michael Chan of the Ohio State Research Foundation in the U.S. will develop an engineered strain of bacteria used to ferment beans in traditional Asian and African diets, to display an antigen from the Tuberculosis bacterium. The engineered bacillus will then be used to make the traditional Asian dish natto, which can serve as a kind of oral vaccine to elicit a strong immune response. If successful, this strategy can be used to introduce a variety of disease antigens through culturally accepted foods.

Sylvia van den Hurk and Sidney Hayes of the University of Saskatchewan in Canada proposes that bacteriophage lambda, a virus that invades bacterial cells and uses the host's genome to replicate, can be used as a vector to deliver DNA vaccines into targeted cells. Van den Hurk will test this lambda delivery platform its ability to induce long-term systemic and mucosal immune responses.

Sergey Shevkoplyas, Lakhinder Kamboj, and Noshir Pesika of Tulane University in the U.S. will develop a microfabricated bidirectional membrane that can be placed in the mother's vagina just prior to delivery to facilitate the baby's passage through the birth canal. This simple-to-use device could significantly improve outcomes during vaginal deliveries in resource limited settings.

Rachel Teitelbaum of Hervana, Ltd. in Israel will develop and test a biological vaginal formulation that produces a sperm-binding agent, which interferes with sperm motility or fertilization or both. It is hoped that this non-hormonal contraceptive will need only infrequent administration to maintain its effectiveness. In this project's Phase I research, Teitelbaum developed a lead formulation and demonstrated initial proof-of-principle that such an approach can provide effective contraception. In Phase II, Teitelbaum and her team will expand upon this proof-of-principle in animal models to arrive at a long-acting, safe, and effective contraceptive that is ready for evaluation in human trials.

David Herrin and colleagues at the University of Texas propose to develop a green-algal food source for mosquito larvae into a biological control agent by engineering their chloroplasts to produce larvacidal proteins. The chloroplast genome has significant advantages for genetic modification, including stability and containment.

Christopher Duggan of Children’s Hospital Boston in the U.S. and his team will test whether known biomarkers of gut dysfunction can accurately predict impaired neurodevelopment and stunting, which reflects chronic malnutrition and is associated with increased morbidity and mortality in young children. The biomarkers will be validated in a well­-characterized group of young Tanzanian children. The goal is to facilitate the identification of at risk children early in life, so that appropriate intervention strategies can be applied.

Clare Elwell of University College London in the United Kingdom is using non-invasive optical brain imaging (near-infrared spectroscopy) to assess cognitive function in malnourished infants and children in low-resource settings over time. The technology is relatively low-cost and portable, and their approach could be used to determine the impact of malnutrition on the developing brain and guide nutrition-related interventions. In Phase I, they performed functional brain imaging in the presence of specific stimuli on 99 infants aged 0-2 years old in a rural setting in The Gambia over a 10-month period. This established proof-of-principle of their approach for measuring brain function in the field. In Phase II, they will expand the study to include 250 infants who will also be evaluated for additional physical, behavioral and cognitive parameters and analyzed every four months. This dataset will then be used to identify markers of disrupted cognitive development for early intervention, to provide insight into the role of malnutrition and other factors such as disease, and to help monitor treatments.

Christine Hrycyna and Jean Chmielewski of Purdue University in the U.S. will develop novel dimeric drugs designed to block a key protein in the malaria parasite that limits the accumulation of anti-malarials in the parasite's digestive system. By inhibiting this protein, this new therapy could eliminate drug resistance in malaria parasites.

Sally Mackenzie of the University of Nebraska-Lincoln in the U.S. will establish a strategy to exploit crop phenotype variations that are controlled by epigenetic changes for breeding. The strategy is to disrupt the MSH1 gene in millet and maize, releasing a large amount of variation derived from heritable epigenetic changes that can be used to select for abiotic and biotic stress tolerance.