Udantha Abeyratne of the University of Queensland in Australia proposes using low-cost devices such as mobile phones and mp3 players equipped with microphones to record cough and sleeping sounds that do not require direct contact with the patient. Recording will be analyzed using new algorithms in human speech analysis to identify sounds that characterize the presence of pneumonia.

Ronald Quinn of Griffith University's Eskitis Institute in Australia and colleagues are seeking to discover chemical fragments drawn from a variety of natural sources that bind to proteins expressed by the malaria parasite in its latent stage and the tuberculosis microorganism. In their Phase I and Phase II research, the team is working on identifying compounds that target proteins involved in key metabolic and energy pathways of latency as the basis for new drug therapies.

Krystal Evans of The Walter and Eliza Hall Institute in Australia will knock out several proteins that support the expression of the major virulence factor for the malaria parasite. Their aim is create a genetically-attenuated live malaria vaccine that elicits a strong immune response against diverse strains of the parasite.

Hongshen Ma of the University of British Columbia in Canada will develop an inexpensive hand-held device consisting of a series of funnels of decreasing size that will separate healthy red-blood cells, which can easily squeeze through openings, from malaria-parasite infected blood cells which become more rigid. A simple integrated optical sensor would then count stained cells in these various stages to determine the state of infection and inform treatment options.

Emmanuel Ho of the University of Manitoba in Winnipeg, Canada will develop a polyether urethane (PU) intra-vaginal ring designed to slowly release the HIV peptide gp120, as well as the cytokine IL-12 as an adjuvant, directly into the vaginal mucosa to stimulate a sustained mucosal immune response.

Abani Nag and Amiya Hati of Vivekananda International Health Centre in India will test the hypothesis that ultrasound measurements of the liver and spleen, as well as functional liver enzyme tests, will to help differentiate cases of relapse versus re-infection of malaria, leading to more appropriate treatment and drug therapies.

Claudia Pastori of Fondazione S. Raffaele del Monte Tabor in Italy seeks to induce mucosal immunity against HIV by using a bacterial adhesive protein to target antigens to specific cells. The goal of this approach is to present conserved epitopes of HIV in their natural form to elicit the production of protective antibodies in the tissues where these antibodies will be effective.

Shahid Khan of Leiden University Medical Centre in the Netherlands seeks to produce a multi-stage malaria vaccine using transgenic sporozoites. These parasite forms will also present transmission blocking antigens to not only generate protective immunity against early stages of infection, but also generate antibodies to block transmission via mosquitoes.

Peter Lubega Yiga of AdhocWorks Foundation in South Africa will test the efficacy of small household containers in which a non-toxic formulation is mixed with water, releasing carbon dioxide and alcohol vapors as a way to repel mosquitos. The investigators will test the device in independent field trials to optimize its usefulness as an alternative to insecticides.

Matthew Fuchter and collaborators at Imperial College London in the United Kingdom proposes to test whether a novel chemical produced in some fungus species can control enzymes that control immune escape mechanisms in malaria parasites. If successful, this approach may not only force the parasite to present many surface proteins that are normally absent and stimulate a powerful immune response, but could also directly kill malaria parasites.

Federica Marelli-Berg of Imperial College London in the United Kingdom will test the theory that using “homing factors” as vaccine adjuvants will induce the development of memory T cells, thereby generating site-specific immunity against pathogens in the gut. This project's Phase I research demonstrated that helminth infection in the presence of a homing factor led to an enhanced immunological effect. In Phase II, Marelli-Berg, now at the Queen Mary University of London, aims to develop this observation into a vaccination protocol for clinical application in this and other infections.

William Royea of Next Dimensions Technology, Inc., in the U.S. seeks to develop a point-of-care breath analyzer. The proposed system aims to use an array of chemical films that are sensitive to changes in electrical conduction as a result of volatile organic compounds (VOCs) produced by tuberculosis (TB). In this project’s Phase I research, Royea and his team demonstrated proof-of-concept for detecting breath-based biomarkers of TB in a clinical setting. In Phase II, the team will further develop and test a prototype device that provides higher sensitivity and specificity to not only identify active TB disease in ill patients, but also potentially to distinguish between various drug-resistant strains of the mycobacterium.

Suzanne Smith of STAR Analytical Services in the United States will study recorded cough samples with acoustic vocalization-analysis technology to identify sound characteristics that indicate specific symptoms of pneumonia with the aim of rapidly identifying the cause and severity of respiratory illness. It is hoped that such acoustic landmarks would help in the differentiation between viral infections and bacterial illnesses, each of which may require different treatments.

Rebecca Richards-Kortum of Rice University in the U.S. will measure light scattered by malaria-infected red blood cells using a small microscope that can be placed on the skin as a way to detect infection in patients without the need to draw blood. This rapid and painless diagnostic would not require consumable reagents or a trained operator, and would not generate biohazardous waste. This project's Phase I research demonstrated that two key optical signatures could be used to recognize malaria-infected red blood cells and that these signatures could be visualized in the superficial vasculature of an animal model with a table-top microscope. In Phase II, Richards-Kortum and a team will develop a portable, battery-powered microscope and test its ability to image the superficial vasculature in humans and also quantify infected red blood cells in a small pilot study of malaria patients.

Scott Phillips, of Pennsylvania State University in the U.S. proposes to develop a polymer reagent to be deposited at the bottom of a small paper cup used to collect a sputum sample, where it will detect proteins secreted by tuberculosis and turn indicate TB-positive samples by changing color.

Changhuei Yang of the California Institute of Technology in the U.S. will evaluate the feasibility of using a "microscope on a chip" along with a hand-held reader to detect and analyze cells and parasites in bodily fluids. If successful; this technology, which does not use traditional lenses, could provide diagnostic capabilities for a wide range of diseases including malaria.

Joseph Vinetz of the University of California, San Diego in the U.S. will attempt to create a new mouse model that mimics both human liver and blood cell function. These new mouse models should allow human malaria parasites to complete their full life cycle in the models and provide a new tool for testing anti-malarial strategies, including drugs and vaccines.

Moriya Tsuji of the Aaron Diamond AIDS Research Center in the U.S. will test whether the human malaria parasite can infect mice engineered with humanized livers and red blood cells by producing human erythropoietin. The goal of this project is part of a larger effort to create a mouse model capable of supporting the full malaria life cycle for use in preclinical testing of new anti-malarial therapies and vaccines.

Michael Riehle of the University of Arizona in the U.S. will manipulate insulin signaling in mosquito tissues to create a new breed of mosquito that has a shorter lifespan, yet has increased fertility. Because only older mosquitoes can transmit the malaria parasite, the team hopes these fertile, short-lived mosquitoes will replace longer-lived malaria carriers.

Daniel Fletcher of the University of California, Berkeley in the U.S. will develop a microscope that attaches to cell phones to capture high-contrast fluorescent images of malaria parasites. Custom software on the phone will automatically count the parasite load, with results and patient information wirelessly transmitted to clinical centers for tracking.

Paul Kim of Johns Hopkins University in the U.S. will modify HIV by removing the viral genome and replacing the outer domain of the gp120 protein, used by the virus to invade host immune cells, with receptors normally used by gp120 to bind to host cells. When this modified ghost virus encounters native HIV during an infection, hidden epitopes are exposed to the host immune system, stimulating antibodies to clear the infection.

Tycho Speaker of Transderm Inc. in the United States, along with Juvaris Biotherapeutics, will test the efficacy of a dry microneedle skin patch loaded with malaria antigens and a novel adjuvant for its ability to stimulate a robust immune response. If successful, this painless, low-cost, no-refrigeration vaccine delivery system could increase vaccine access to at-risk populations.

William Gordon and collaborators at Tetragenetics, Inc. in the U.S. propose using T. thermophilia, a fresh-water protozoa commonly used in basic research, to produce malaria antigens in a crystalline protein gel. The close evolutionary relationship between T. thermophilia and protozoan malaria parasites may allow the antigens to retain their natural conformation. In this way, multiple vaccine components can be readily harvested as a single, low-cost, high-potency vaccine formulation. This project's Phase I research demonstrated that T. thermophilia can be used to develop anti-malarial transmission blocking vaccines. In Phase II, Marco Cacciuttolo will lead a team of collaborators to further research the production and immune stimulating effects of multi-antigen and adjuvant formulations that could be used in a low-cost, long-lasting malaria vaccine.

Because HIV infection activates naturally-dormant endogenous retroviruses (ERV) in human cells, Jonah Sacha will target T cells against these ERV antigens. Such targeting to eliminate HIV infected cells could be the basis for new host-directed vaccines. In this project’s Phase I research, Sacha and collaborators demonstrated that ERV-specific antibodies are specifically triggered by infection with an exogenous retrovirus like SIV or HIV. In Phase II, Sacha, now at the Oregon Health & Science University in the U.S., will investigate whether ERV-specific antibodies can block transmission of AIDS viruses in animal models, leading to their potential use as a therapeutic and prophylactic vaccine.

Yingjie Lu and Richard Malley of Children's Hospital Boston in the U.S. will develop a bivalent pneumococcal and typhoid vaccine by using a new technology to include three highly conserved pneumococcal antigens and the well-established Vi polysaccharide antigen that provides protection against typhoid fever. The team will test the ability of this vaccine to induce strong humoral and cellular immune responses against both pneumococcus and the causative agent of typhoid fever, Salmonella Typhi. In this project’s Phase I research, the team successfully developed the bivalent vaccine and in initial research was able to demonstrate dual immunity to both pneumococcus and S. Typhi. In Phase II, they will perform further proof-of-concept experiments in animal models that will provide support for the clinical development of this bivalent vaccine candidate.

Kailash Patra of the University of California, San Diego in the U.S. will use proteomics to examine gametocyte, zygote, or ookinete surface proteins of the malaria parasite to test their reactivity to human serum collected from malaria endemic regions, and to identify new antigen candidates for malaria vaccines.

Jinhee Lee and Gary Ostroff of the University of Massachusetts Medical School in the U.S. will test the idea of delivering small interfering RNA (siRNAs) via glucan particles in an oral TB vaccine formulation. The team will utilize the siRNAs' ability to block immunosuppressive signaling and amplify the immune response.

Craig Morita of the University of Iowa in the U.S. will engineer Salmonella and Shigella vaccine vectors to overproduce an essential antigen to stimulate gamma delta T cells, to boost mucosal immune response against these enteric pathogens.

David Schwartz of Hackensack University Medical Center in the U.S. will test an intradermal injection that increases levels of vitamin A and blocks vitamin D3 metabolism. These important mechanisms can “educate” B cells to home to the gut and to make mucosal antibodies against many viruses, including HIV.

Renjie Chang of Lavax, Inc. in the U.S. has developed a natural food substance that reduces HIV viruses in the mother's milk, and will test it along with scientists at University of Toledo for its ability to block HIV transmission from mothers to infants.

Ranjan Nanda and Virander Chauhan of the International Centre for Genetic Engineering & Biotechnology in India will gather breath samples from tuberculosis patients and use gas chromatography-mass spectrometry (GC-MS) to identify and track unique molecules such as volatile organic compounds (VOCs) that might serve as biomarkers to diagnose tuberculosis. The overall goal is to then create a handheld "electronic nose" to diagnose the disease in resource-poor settings. The project's Phase I research demonstrated that although no single VOC could be used as a biomarker to diagnose TB, there are key molecules in breath that do vary based on TB exposure and disease's level of activity. In Phase II, Nanda will refine the biomarker signature to diagnose TB and test the ability of the portable "electronic nose" diagnostic tool equipped with a sensor array to specifically detect these key molecules in TB patients in India.

Tanapat Palaga of Chulalongkorn University in Thailand seeks to create a novel DNA vaccine delivery system that targets dendritic cells in GI mucosal tissues. Using chitosan nanoparticles to encapsulate DNA plasmid and protect it from stomach acid, this potential vaccine construct will contain both an antigen and an autophagy- inducing gene to enhance the vaccine's efficacy.

Juan Santiago of Stanford University in the U.S. will develop small, disposable diagnostic device that utilizes isotachophoresis, a technique that separates charged particles, to concentrate a key biomarker of malaria parasites. The goal of this technique is to provide test results within three minutes at a sensitivity much greater than current tests, allowing for detection of malaria at much earlier stages of infection and in asymptomatic individuals.

Allison Ficht of Texas A&M Health Science Center in the U.S. will develop a new TB immunization delivery system based on the protein used by parasitic worms to seal their egg case. This “sticky coating” for nanoparticle vaccines could protect antigens during intranasal administration, affix them to the nasal mucosa and erode in a controlled way to slowly release antigens for enhanced immune response against tuberculosis.

Christopher Pilcher of the University of California, San Francisco in the U.S. will test the theory that HIV proteins, nucleic acids and antibodies to HIV can be detected in shafts of hair. This possible approach may provide a low-cost tool to determine the timing of HIV infection, which is essential to establish incidence rates in populations.

Lourival Possani of the Institute of Biotechnology at the National University of Mexico will investigate the antimalarial effects of scorpine, a newly identified peptide found in the venom of scorpions. The team will test scorpine's efficacy in blocking K+ channels used by malaria parasites to replicate in mosquitoes. Creating a new generation of malaria-resistant mosquitoes can aid in the eradication of the disease in humans.

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.

Viktor Vegh of The University of Queensland in Australia will test the efficacy of using low-cost nuclear magnetic resonance technologies that take advantage of earth's magnetic field to detect malaria parasites. The team will examine blood samples to detect hemozoin, a waste product of malarial parasites, to determine the presence of malaria infection

A high HIV mutation rate enables escape from powerful immune responses and anti-retroviral drugs. Reuben Harris of the University of Minnesota in the U.S. will test the hypothesis that HIV requires the human APOBEC3G protein to maintain a high mutation rate necessary for HIV survival. Inhibiting this protein may slow the mutation rate and make the virus more susceptible to immune responses.

People born with a genetic mutation in their CCR5 gene are naturally resistant to HIV infection. Philip Gregory of Sangamo BioSciences, Inc. in the U.S. will use zinc finger nuclease technology to specifically disrupt the CCR5 gene as a new strategy to make people resistant to HIV.

Recent evidence suggests that HIV infection may be drastically enhanced when a specific protein found in human semen is present in fibril form. David Eisenberg of UCLA in the U.S. will design and test a small peptide that can effectively block formation of fibrils on this protein. If successful, the therapy could be administered via spray or liquid drops to inhibit transmission of HIV.

Louis Schofield of The Walter and Eliza Hall Institute in Australia will develop a synthetic saccharide-conjugated vaccine that would provide immunity against GPI, a toxin produced by the malaria parasite that is a major determinant in the severity and fatality of the disease. This project's Phase I research demonstrated preclinical safety and efficacy of a synthetic anti-toxin vaccine for malaria, showing that the oligosaccharide target was conserved across all malaria species and life stages. In Phase II, Schofield is extending the preclinical evaluation of efficacy of this candidate vaccine against other species and life stages.

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.

Because malnutrition, micronutrient deficiency and parasitic worm infection are all major risk factors for developing visceral leishmaniasis, Dinesh Mondal of International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) will study if VL development can be prevented in asymptomatic patients through nutritional supplements of vitamin A, zinc and iron, as well as anti-helminth treatment.

Gustavo Fioravanti Vieira of Universidade Federal do Rio Grande do Sul in Brazil will create 3-D computer models of viral epitopes anchored to major histocompatibility complex (MHC) molecules associated with different MHC alleles to search for “generalist” epitopes. Such epitopes can be used to develop viral vaccines that are effective against a broad spectrum of pathogens.

Guang-hong Tan of Hainan Provincial Key Laboratory of Tropical Medicine in China seeks to create a next-generation malaria vaccine by deleting a gene responsible for parasite development in the liver adding a new gene which attracts dendritic cells to the infection site. Using this modified sporozoite in a vaccine could produce a limited infection that, at the same time, induces a strong immune response against malaria.

In organisms that have extreme mutation rates, such as RNA viruses, quasispecies are highly diverse genotypes that may drastically differ from the general population and often become less viable as they continue to mutate. Using new deep sequencing technology, Marco Vignuzzi of the Pasteur Institute in France hopes to identify such RNA viruses that have managed to retain attenuated strains in order to study these genotypes for possible use in the development of viral vaccines.

HIV uses the CCR5 co-receptor protein found in mammals as a major pathway to enter target cells. Because some patients who are exposed, yet resistant, to the virus, or have HIV but do not ever progress to AIDS can exhibit the presence of CCR5 internalizing antibodies, Lucia Lopalco of the San Raffaele Scientific Institute in Italy will attempt to generate “anti-self” antibodies against CCR5 to knock out protein's co-receptor and effectively block HIV entry.

Oladele Akogun of the Common Heritage Foundation in Nigeria seeks to develop a “fever kit” for use among nomadic populations to help them accurately diagnose and treat fevers in a way that reduces mortality and drug resistance. The device will be equipped with simple diagnostic tools and prerecorded treatment instructions in the native language to help nomadic caregivers distinguish between malaria and other causes of fevers, and will also contain drug treatments appropriate to the diagnosed illness.