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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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Reawakening Retrocyclins to Combat Mucosal STIs in Women

Alexander ColeUniversity of Central Florida Research FoundationOrlando, Florida, United States
Grand Challenges Explorations
Mucosal Immunity
16 Nov 2009

Alexander Cole of the University of Central Florida will attempt to restore natural expression of retrocyclins, antiviral peptides whose production in humans has been latent for millions of years. Cole will test inexpensive and widely available antibiotics for their ability to induce production of these retrocyclins, leading to its possible use as a vaginal microbicide.

Diagnosis of Pneumonia Using Sound Recordings

Udantha AbeyratneUniversity of QueenslandBrisbane, Queensland, Australia
Grand Challenges Explorations
Diagnostics
1 Nov 2009

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.

A Novel Virulence-Associated Malaria Drug Target

Paul GilsonBurnet InstituteMelbourne, Victoria, Australia
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

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.

New Screening Technologies for Drug Discovery of Latent Malaria Infections

Ronald QuinnGriffith UniversityBrisbane, Queensland, Australia
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

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.

Vaccine for HIV Using a Novel Mucosal Vector and Adjuvant

Stephen KentUniversity of MelbourneMelbourne, Victoria, Australia
Grand Challenges Explorations
Vaccines
1 Nov 2009

Stephen Kent and John Stambas of the University of Melbourne in Australia will develop and test an attenuated influenza virus vector with an adjuvant that stimulates natural killer cells. The goal of this approach is to induce robust immunity at mucosal surfaces to HIV, which is important in both prevention and control of infection.

Development of a Genetically-Attenuated Live Malaria Vaccine

Krystal EvansThe Walter and Eliza Hall Institute of Medical ResearchVictoria, Victoria, Australia
Grand Challenges Explorations
Vaccines
1 Nov 2009

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.

Using Exercise to Improve Pneumococcal Vaccine Efficiency

Kate EdwardsThe University of SydneySydney, New South Wales, Australia
Grand Challenges Explorations
Vaccines
1 Nov 2009

Kate Edwards of University of Sydney in Sydney, Australia will test the theory that brief bouts of exercise consisting of cycling and weight lifting will increase antibody and cell-mediated responses to a pneumococcal vaccination administered immediately after the physical activity.

Microfluidic Isolation of Red Cells Infected With Malaria

Hongshen MaUniversity of British ColumbiaVancouver, British Columbia, Canada
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

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.

Dendritic Cell Receptor-Targeted Malaria Vaccines

Rajan GeorgePaladin BiosciencesEdmonton, Alberta, Canada
Grand Challenges Explorations
Vaccines
1 Nov 2009

Rajan George of Paladin Biosciences, a division of Paladin Labs Inc. in Canada will produce a vaccine with multiple malaria antigens to target dendritic cell receptors and without the need for an adjuvant, in an effort to induce both antibody and cell-mediated immune responses to the malaria parasite at various stages of the infection.

New Intravaginal Delivery System to Induce Mucosal Immunity

Emmanuel HoUniversity of ManitobaWinnipeg, Manitoba, Canada
Grand Challenges Explorations
Mucosal Immunity
1 Nov 2009

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.

Artificial Triggering of Malaria Parasite Relapse

Lena HuldenUniversity of HelsinkiHelsinki, Finland
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

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.

Electronic Nose to Smell Tuberculosis from Breath VOCs

Ranjan NandaInternational Centre for Genetic Engineering and BiotechnologyNew Delhi, , India
Grand Challenges Explorations
Diagnostics
1 Nov 2009

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.

Finding Malaria Relapse Using Liver Function Tests

A. NagVivekananda International Health CentreKolkata, West Bengal, India
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

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.

Develop Novel Receptor Blocking Vaccines Against P. falciparum and P. viva

Deepak GaurInternational Centre for Genetic Engineering and BiotechnologyNew Delhi, , India
Grand Challenges Explorations
Vaccines
1 Nov 2009

Deepak Gaur, Chetan Chitnis and Virander Chauhan of the International Centre for Genetic Engineering & Biotechnology in India will attempt to develop a blood- stage malaria vaccine that uses a combination of two proteins found among a wide diversity of malaria parasites. Their goal is to stimulate antibodies that would stop parasite infection of red blood cells by blocking multiple pathways of invasion.

Light-Activated Pellets for Mosquito Larvae Control

Annette HabluetzelUniversity of CamerinoCamerino (MC), Italy
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

Annette Habluetzel of the University of Camerino in Italy seeks to develop a micropellet food for mosquito larvae made from non-toxic, organic compounds. These pellets, when ingested by the transparent larvae are activated by sunlight and kill the larvae, leaving other animals unharmed.

Induction of HIV Protective Mucosal Antibodies

Claudia PastoriFondazione Centro San Raffaele del Monte TaborMilan, Italy
Grand Challenges Explorations
Mucosal Immunity
1 Nov 2009

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.

Malaria Diagnosis Using Iron and Plasma

Jackie ObeyUniversity of Eastern Africa, BaratonEldoret, Kenya
Grand Challenges Explorations
Diagnostics
1 Nov 2009

Jackie Obey of the University of Eastern Africa, Baraton in Kenya will test the efficacy of a diagnostic test for malaria in which small amounts of blood are mixed with an iron solution to create vibrant colors that indicate the amount of a protein released by the malaria parasite.

Preventing Malaria in Both Host and Vector

Shahid KhanLeiden University Medical CenterLeiden, Netherlands
Grand Challenges Explorations
Vaccines
1 Nov 2009

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.

Sublingual Vaccination for Inducing Broad-Based Mucosal Immunity

Cecil CzerkinskyInternational Vaccine InstituteSeoul, South Korea
Grand Challenges Explorations
Mucosal Immunity
1 Nov 2009

Cecil Czerkinsky of the International Vaccine Institute in South Korea will test the efficacy of administering two approved vaccines sublingually – directly under the tongue. The team will attempt to produce not only antibody responses but also cytotoxic T cell responses in distant mucosal organs such as the lungs and reproductive tract. Sublingual vaccine administration could help improve vaccine delivery, compliance, and enhance immunity against a variety of pathogens.

Fermentation Based Mosquito Repelling Device

Peter YigaAdhocWorks CCJohannesburg, South Africa
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

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.

Maternal Immunization to Protect Infants Against Malaria

Margaret NjorogeMed Biotech LaboratoriesKampala, Uganda
Grand Challenges Explorations
Vaccines
1 Nov 2009

Margaret Njoroge and Thomas Egwang of Med Biotech Laboratories in Uganda will develop and test an intranasal vaccine to be administered to young women before pregnancy, and again after childbirth, to confer anti-malarial immunity in their babies.

Targeting of the P. falciparum Immune Evasion Mechanism

Matthew FuchterImperial College LondonLondon, United Kingdom
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

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.

Targeting Malaria Hotspots In Rural Poorly Resourced Settings

Roly GoslingLondon School of Hygiene and Tropical MedicineLondon, United Kingdom
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

Roly Gosling of the London School of Hygiene and Tropical Medicine in the United Kingdom will conduct a pilot study in Tanzania to test whether malaria cases can be contained by treating the households and immediate neighbors of those diagnosed with malaria. The goal of this research is to understand whether such community approaches can clear asymptomatic carriers and eliminate parasites within these “hotspots.”

Programming T cell Homing to Induce Gut-Selective Immunity

Federica Marelli-BergImperial College LondonLondon, United Kingdom
Grand Challenges Explorations
Mucosal Immunity
1 Nov 2009

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.

New Whole-Species Pneumococcal Vaccines

Jeremy WebbUniversity of SouthamptonSouthampton, United Kingdom
Grand Challenges Explorations
Mucosal Immunity
1 Nov 2009

Jeremy Webb and collaborators at the School of Biological Sciences in the United Kingdom will search for unique proteins that allow pneumococcal bacteria to form biofilms on mucosal surfaces. The team will use laser capture micro-dissection “laser tweezers” to dissect these bacterial communities with the goal of finding antigens common to all serotypes and could be used as the basis for future vaccines.

Electrical Detection of TB Signals in Breath

William RoyeaNext Dimension Technologies, Inc.Pasadena, California, United States
Grand Challenges Explorations
Diagnostics
1 Nov 2009

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.

"Coffee Ring Stain" Diagnostics for Malaria

David WrightVanderbilt UniversityNashville, Tennessee, United States
Grand Challenges Explorations
Diagnostics
1 Nov 2009

David Wright of Vanderbilt University in the U.S. will develop a new low-cost diagnostic tool in which a droplet of malaria-infected blood deposited on a glass slide will, based on fluid dynamics, leave a ring-like pattern as the blood evaporates. The slide will be prepared with a solution that will interact with a particular protein of the malaria parasite to visualize this "coffee ring stain," allowing for easy interpretation and ready diagnosis.

Using Acoustic Analysis of Cough to Diagnosis Pneumonia

Suzanne SmithSTAR Analytical ServicesBedford, Massachusetts, United States
Grand Challenges Explorations
Diagnostics
1 Nov 2009

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.

MALiVA: A Malaria Immunodiagnostic for Saliva-borne Antigens

Andrew FungUniversity of California, Los AngelesLos Angeles, California, United States
Grand Challenges Explorations
Diagnostics
1 Nov 2009

Andrew Fung, Jack Judy and Theodore Moore at the University of California, Los Angeles in the U.S., along with Michel Bergeron of l'Université Laval in Canada, will work to identify molecular markers of malaria present in saliva in order to develop a chewing gum diagnostic tool called “MALiVA.” During chewing, particles in the gum will react with these malaria proteins, which can be detected and characterized when this device is scanned with a magnet.

Reagent-Free, Needle-Free Microscopy for Malaria Diagnosis

Rebecca Richards-KortumRice UniversityHouston, Texas, United States
Grand Challenges Explorations
Diagnostics
1 Nov 2009

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.

Infrared Signature of Malaria Infection

Wei LuUniversity of MichiganAnn Arbor, Michigan, United States
Grand Challenges Explorations
Diagnostics
1 Nov 2009

Wei Lu of the University of Michigan in the U.S. will test the theory that red blood cells infected with malaria have significantly different characteristics when subjected to light in ultra-far infrared spectrum. Using these techniques, this project aims to develop a non-invasive tool to scan capillaries near the body surface and diagnose malaria.

Highly Sensitive TB Detection using a Paper Cup

Scott PhillipsPennsylvania State UniversityUniversity Park, Pennsylvania, United States
Grand Challenges Explorations
Diagnostics
1 Nov 2009

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.

Malaria Diagnostics on Skin

Howard BernsteinSeventh Sense BiosystemsCambridge, Massachusetts, United States
Grand Challenges Explorations
Diagnostics
1 Nov 2009

Howard Bernstein of Seventh Sense Biosystems in the U.S. will engineer a skin patch that can detect and measure malaria proteins in interstitial fluid. If successful, an easy-to-use biocompatible device may be able to allow continued monitoring of infection for a few weeks, instead of a single time point.

Lensless Microscope for Diagnostics

Changhuei YangCalifornia Institute of TechnologyPasadena, California, United States
Grand Challenges Explorations
Diagnostics
1 Nov 2009

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.

Bacterial Viruses as Tool for Blocking Transmission of Malaria

Luiz OzakiVirginia Commonwealth UniversityRichmond, Virginia, United States
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

Luiz Ozaki and Gail E. Christie of Virginia Commonwealth University in the U.S. will genetically engineer bacterial viruses to carry peptides that block the development of the malaria parasites, survive in the mosquito gut, and spread through vector populations. If successful, these bacteriophages could be used as “gene dissemination tools” for effective control of the malaria.

Humanized Mouse: Recapitulate P. falciparum/vivax Cycle

Joseph VinetzUniversity of California, San DiegoSan Diego, California, United States
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

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.

An Endothelial Reservoir for Malaria?

Michael LeibowitzRobert Wood Johnson Medical SchoolPiscataway, New Jersey, United States
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

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.

Humanized Mouse Model for Malaria Research

Moriya TsujiThe Aaron Diamond AIDS Research CenterNew York, New York, United States
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

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.

Identifying Drugs to Block Transmission

Matthias MartiHarvard UniversityCambridge, Massachusetts, United States
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

Matthias Marti of the Harvard School of Public Health in the U.S. will utilize a newly developed transgenic malaria parasite that expresses GFP indicating when the parasites are ready to be transmitted to mosquitoes. He will use this technology to screen for compounds that can prevent the development of these gametocytes.

Manipulating the Mosquito's Lifespan to Control Malaria

Michael RiehleUniversity of Arizona FoundationTucson, Arizona, United States
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

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.

An Immunity-Enhancing Beverage

Steven MaranzCornell UniversityIthaca, New York, United States
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

Steven Maranz of Weill Medical College in the U.S. will test the hypothesis that providing children high levels of flavanols, compounds found in chocolate, green tea, cola and shea nuts, deprives malaria parasites of lipids needed to survive, keeping parasite infection at levels low enough to elicit a strong immune response that builds lifelong immunity.

Cell Phone Microscopy for Malaria Diagnosis

Daniel FletcherUniversity of California, BerkeleyBerkeley, California, United States
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

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.

Drugs That Inhibit Malaria Infection and Block Transmission

Victor NussenzweigNew York UniversityNew York, New York, United States
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

Victor Nussenzweig of the New York University School of Medicine in the U.S. seeks to develop a small molecule drugs to inhibit key kinase enzymes in the malaria parasite that are thought to control latency in parasite infections. Such fundamental knowledge may enable new tools to clear the latent forms of P. vivax parasites or block transmission of the disease by targeting sporozoites.

Ghost HIV Virus to Stimulate the Immune System

Paul KimJohns Hopkins UniversityBaltimore, Maryland, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

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.

A Novel Approach of Creating an Attenuated Pneumonia Vaccine

Vijay PancholiOhio State University Research FoundationColumbus, Ohio, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

Vijay Pancholi of The Ohio State University Research Foundation in the U.S. will attempt to attenuate the S. pneumonia bacteria by altering export of the GAPDH enzyme, a function thought to be essential to the bacteria's survival. Preventing export of this key enzyme will decrease bacterial virulence, allowing the attenuated strain to be used for development an affordable live vaccine for pneumococcal pneumonia.

Inexpensive, Dry, Heat-Stable, Vaccine Skin Patch

Tycho SpeakerTransDerm, Inc.Santa Cruz, California, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

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.

Synthetic Peptides to Inhibit HIV Entry

Chang Yi WangUnited Biomedical, Inc.Hauppauge, New York, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

Chang Yi Wang of United Biomedical, Inc. in the United States will develop and test synthetic peptide immunogens that mimic conserved sites used by HIV to gain entry to host T-cells. Mimicking the correct three-dimensional structure of these important proteins should generate antibody responses that block this initial step of HIV infection and neutralize the virus.

Using Common Freshwater Protozoa to Produce Malaria Vaccines

William GordonTetragenetics, Inc.Ithaca, New York, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

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.

Vaccines Against Diarrhea Causing Gram Negative Bacteria

Sangeeta JoshiUniversity of Kansas Center for ResearchLawrence, Kansas, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

Sangeeta Joshi of the Middaugh laboratory at the University of Kansas in the U.S. will develop a novel polymer vaccine composed of assembled versions of “needle” and “tip” surface proteins used by Shigella and Salmonella pathogens to trigger bacterial invasion in human intestinal cells, and test it for its ability to induce antibody response.

Genetic Fossils Used As Vaccine Targets for HIV

Jonah SachaOregon Health and Science UniversityPortland, Oregon, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

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.

Low-Cost Multivalent Pneumococcal Vaccine

Kevin KilleenMatrivax, Inc.Boston, Massachusetts, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

Kevin Killeen of Matrivax R&D Inc. in the U.S. proposes applying a novel technology which entraps many polysaccharide antigens in a protein matrix. If successful, this prototype platform could increase the breadth of serotypes currently covered by pneumococcal vaccines as well as reduce costs of vaccine production.

A Single Vaccine Against Pneumococcus and Typhoid Fever

Yingjie LuChildren's Hospital BostonBoston, Massachusetts, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

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.

Engineered H. pylori as a Diarrheal Vaccine Platform

Martin BlaserNew York UniversityNew York, New York, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

Martin Blaser of the New York University School of Medicine in the U.S. proposes to engineer a harmless modification of H. pylori, a bacteria commonly found in the human stomach, to deliver antigens to protect against intestinal pathogens such as cholera and campylobacter. This modified H. pylori can only survive in the presence of an enzyme supplied in special drinking water, allowing those administering the vaccine to regulate its colonization.

Malaria Transmission Blocking Vaccines (TBV) Boosted By Natural Exposure

Kailash PatraUniversity of California, San DiegoSan Diego, California, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

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.

Transmission-Blocking Vaccine Based on Malaria Gamete Surface Protein

Nirbhay KumarTulane UniversityNew Orleans, Louisiana, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

Nirbhay Kumar of Johns Hopkins University in the U.S. will use a technique called codon harmonization to fully and correctly express a complex malaria gamete surface protein. The sexual stages of malaria parasites have been shown to be particularly vulnerable to antibody targeting. This approach may be able to block the transmission of malaria in insect vectors.

Enhancing TB Vaccines with Gene Silencing

Jinhee LeeUniversity of MassachusettsWorcester, Massachusetts, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

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.

Potentiating Mucosal Vaccines by RANKL Induction of M Cells

Ifor WilliamsEmory UniversityAtlanta, Georgia, United States
Grand Challenges Explorations
Mucosal Immunity
1 Nov 2009

Ifor Williams of Emory University School of Medicine in the U.S. will test the theory that a newly characterized cytokine that triggers the development of M cells can be used as an adjuvant to boost immunity in mucosal surfaces and lead to greater uptake of vaccines.

Metabolic Engineering of Salmonella and Shigella Vaccines

Craig MoritaUniversity of IowaIowa City, Iowa, United States
Grand Challenges Explorations
Mucosal Immunity
1 Nov 2009

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.

Targeted Oral Vaccines to Induce Cellular & Mucosal Immunity

Jennifer MaynardThe University of Texas at AustinAustin, Texas, United States
Grand Challenges Explorations
Mucosal Immunity
1 Nov 2009

Jennifer Maynard and Nicholas Peppas of the University of Texas at Austin in the U.S. seeks to engineer proteins to be delivered by oral polymeric vaccine that specifically bind to receptors of M cells on the gut mucosa. By targeting these M cells, antigens can be introduced directly to the mucosal system, inducing a targeted, stronger immune response.

Vitamin A to Induce Gut Homing of Immune Cells

David SchwartzHackensack University Medical CenterHackensack, New Jersey, United States
Grand Challenges Explorations
Mucosal Immunity
1 Nov 2009

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.

Intestinal Alkaline Phosphatase to Treat and Prevent Diarrhea

Madhu MaloGeneral Hospital CorporationBoston, Massachusetts, United States
Grand Challenges Explorations
Mucosal Immunity
1 Nov 2009

Madhu Malo of Massachusetts General Hospital/Harvard Medical School in the U.S. will investigate whether maintaining the normal intestinal commensal bacteria using oral supplementation of intestinal alkaline phosphatase (IAP), a small intestinal brush-border enzyme, will prevent or cure infection by pathogenic bacteria. A successful project would generate a universal prophylactic and therapeutic strategy against diarrheal diseases.

Novel Method Protecting Infants from HIV in Breast Milk

Renjie ChangLavaxPalantine, Illinois, United States
Grand Challenges Explorations
HIV Infection
1 Nov 2009

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.

Pre-Season Elimination of Malaria Infections

Sungano MharakurwaMalaria Institute at MachaChoma, Zambia
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

Sungano Mharakurwa of the Malaria Institute in Zambia proposes to take advantage of the “off-season” in regions affected by malaria. The team will identify asymptomatic carriers of the malaria parasite using a simple, non-invasive diagnostic tool using saliva samples which can be easily used by village community workers. Those individuals will be treated to eliminate the parasite before it can be transmitted during the rainy season, when malaria cases increase.

Inducing Autophagy in Dendritic Cells By DNA Delivery

Tanapat PalagaChulalongkorn UniversityBangkok, Thailand
Grand Challenges Explorations
Mucosal Immunity
9 Oct 2009

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.

Eradication of Malaria through the Development of Host Directed Therapy

Simon FooteMenzies Research InstituteDarwin, Northern Territory, Australia
Grand Challenges Explorations
Malaria Eradication
8 Oct 2009

Simon Foote of the Menzies Research Institute at the University of Tasmania in Australia will use "forward genetic screening" approaches identify mutations that confer resistance after exposure to malaria parasites. The team will use this powerful information to develop drug therapies that target the human host and mimic these protective genetic effects.

Highly Sensitive, Low-Cost Malaria Test

Juan SantiagoStanford UniversityStanford, California, United States
Grand Challenges Explorations
Diagnostics
8 Oct 2009

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.

Improving the Immunogenicity of HIV Envelope Glycoproteins

Michel GilbertNational Research Council of CanadaOttawa, Ontario, Canada
Grand Challenges Explorations
Vaccines
7 Oct 2009

Michel Gilbert of the National Research Council Canada will use the single-celled microorganism T. acidophilum to produce HIV proteins with unique sugar residues found only in archaebacteria such as T. acidophilum. By modifying these glycan structures to ones not recognized by humans, Gilbert hopes to elicit a stronger immune response against the virus.

Nanoparticle Mucosal Vaccine Platform from Eggshell Proteins

Allison FichtTexas A&M Health Science CenterCollege Station, Texas, United States
Grand Challenges Explorations
Mucosal Immunity
7 Oct 2009

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.

Excreting HIV Using Antibodies

Edward DolkUtrecht UniversityUtrecht, Netherlands
Grand Challenges Explorations
Mucosal Immunity
6 Oct 2009

Edward Dolk of Utrecht University in the Netherlands proposes using two-sided antibodies, which bind to HIV and to transport receptors in the epithelium. Binding these receptors will cause excretion of the HIV particles outside of the body, thereby reducing viral load.

HIV Incidence Testing in Hair

Christopher PilcherUniversity of California San FranciscoSan Francisco, California, United States
Grand Challenges Explorations
Diagnostics
6 Oct 2009

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.

PlasmoTrack: Spatiotemporal Tracking of Malaria Parasites

Bryan GreenhouseUniversity of California San FranciscoSan Francisco, California, United States
Grand Challenges Explorations
Malaria Eradication
6 Oct 2009

Bryan Greenhouse of the University of California, San Francisco, will design a series of microsatellites, short DNA repeats which have variable lengths in different parasites, to track individual parasites in two regions close to malaria elimination. If successful, this approach will provide insight into parasite transmission networks and help to guide future malaria eradication efforts.

K+ Channel Blockers for Malaria Control

Lourival PossaniNational University of MexicoCuernavaca, Mexico
Grand Challenges Explorations
Malaria Eradication
5 Oct 2009

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.

A Novel Effective Vaccine Against Cholera

Michael LebensUniversity of Gothenburg Institute for Vaccine ResearchGothenburg, Sweden
Grand Challenges Explorations
Vaccines
5 Oct 2009

Michael Lebens of the University of Gothenburg Institute for Vaccine Research in Sweden proposes to develop a new oral cholera vaccine using a single cholera strain that expresses antigens for both the Inaba and Ogawa serotypes and produces cholera toxin subunits that act as an adjuvant to stimulate mucosal immune activity. In this project’s Phase I research, Lebens and his team successfully generated potential vaccine candidate strains that express both Ogawa and Inaba type antigens simultaneously. They also demonstrated in an animal model that oral immunization with these bacteria in a killed formulation elicited immune responses similar to those obtained by vaccination with currently licensed oral killed whole-cell cholera vaccines. In Phase II, he will further improve these strains by inducing them to express an accompanying adjuvant and conduct immunogenicity analyses and other work to prepare for a Phase I trial.

A New Tool for Anti-Malarial Target Gene Validation

Philip ShawNational Center for Genetic Engineering and BiotechnologyPathumthani, Thailand
Grand Challenges Explorations
Malaria Eradication
5 Oct 2009

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.

Microalgal Mediated Eradication of Malarial Mosquito Larvae

Richard SayreDonald Danforth Plant Science CenterSt. Louis, Missouri, United States
Grand Challenges Explorations
Malaria Eradication
1 Oct 2009

Richard Sayre of Donald Danforth Plant Science Center in the U.S. will develop and test a transgenic algae that delivers interference RNA (RNAi) elements to mosquito larvae when they feed on it. These RNAi will silence essential genes used by the larvae to develop, thus killing mosquitoes before they can transmit malaria.

Malaria Detection Using Earth's Magnetic Field

Viktor VeghUniversity of QueenslandBrisbane, Queensland, Australia
Grand Challenges Explorations
Malaria Eradication
30 Sep 2009

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

Breastmilk shield to prevent HIV transmission

Gadi BorkowCupron, Inc.Richmond, Virginia, United States
Grand Challenges Explorations
HIV Infection
1 May 2009

Gadi Borkow of Cupron, Inc. in the U.S. will study the efficacy of using newly developed copper-oxide based filters that deactivate a wide range of viruses, including HIV-1, as a shield to enable HIV-infected mothers to breastfeed their infants without risking transmission of the virus.

Mortalizing HIV – A Novel Method to Help Eradicate HIV

Reuben HarrisUniversity of MinnesotaMinneapolis, Minnesota, United States
Grand Challenges Explorations
HIV Infection
1 May 2009

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.

Using Materials Science to Stop HIV Sexual Transmission

Patrick KiserUniversity of UtahSalt Lake City, Utah, United States
Grand Challenges Explorations
HIV Infection
1 May 2009

Patrick Kiser of the University of Utah in the U.S. will design a vaginal gel that blocks HIV by becoming impermeable in response to the pH change induced by the presence of semen, and includes a polymer engineered to bind to HIV surface proteins to halt viral transport to susceptible tissues and HIV target cells. In this project's Phase I research, Kiser and his team engineered a synthetic polymer that has many of the properties of mucus, and demonstrated that the polymers slow or stops the movement of cells in the presence of semen. In Phase II, Kiser will focus on developing a pericoital contraceptive gel that will prevent the movement of spermatozoa into the uterus.

Zinc Finger Nucleases For in vivo Treatment of HIV Infection

Philip GregorySangamo BioSciences IncRichmond, California, United States
Grand Challenges Explorations
HIV Infection
1 May 2009

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.

A Non-Pathogenic Chimeric THLV-1/HIV-1 Viral Genome as a Model to Study Superinfection Restriction

Kuan-Teh JeangNational Institutes of HealthBethesda, Maryland, United States
Grand Challenges Explorations
HIV Infection
1 May 2009

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.

A Small Molecule That Blocks Male-to-Female Sexual Transmission of HIV

David EisenbergUniversity of California, Los AngelesLos Angeles, California, United States
Grand Challenges Explorations
HIV Infection
1 May 2009

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.

A Self-Adjuvanting Vaccine for ST-ETEC

Roy Robins-BrowneUniversity of MelbourneMelbourne, Victoria, Australia
Grand Challenges Explorations
Vaccines
1 May 2009

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.

Development of a Synthetic Anti-Toxic Vaccine for Malaria

Louis SchofieldThe Walter and Eliza Hall Institute of Medical ResearchVictoria, Victoria, Australia
Grand Challenges Explorations
Vaccines
1 May 2009

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.

Liposomal Dendiritc-Cell (DC)-Targeted Vaccines for TB

Ines AtmosukartoLipotek Pty LtdCanberra, Australian Capital Territory, Australia
Grand Challenges Explorations
Vaccines
1 May 2009

Ines Atmosukarto of Lipotek Pty Ltd. in Australia proposes to develop a novel TB vaccine utilizing synthetic “nano-sacs” called liposomes that carry TB antigens and are anchored with a self-adjuvanting protein that binds to and stimulates dendritic cells.

An Altruistic Vaccine for Mosquito Transmitted Pathogens

Paul YoungUniversity of QueenslandBrisbane, Queensland, Australia
Grand Challenges Explorations
Infectious Diseases
1 May 2009

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.

MicroCubes as Vaccines for the Developing World

Fasseli CoulibalyMonash UniversityClayton, Victoria, Australia
Grand Challenges Explorations
Infectious Diseases
1 May 2009

Fasséli Coulibaly of Monash University in Australia will design a vaccine platform based on protein crystals (MicroCubes) produced by insect viruses to produce new and more potent vaccines with increased stability, obviating the need for refrigerated storage. The crystal structure will be engineered to present multiple antigens that will then be tested for their ability to induce an effective immune response. In Phase I, a proof-of-concept study was performed to establish MicroCubes as a promising vaccine platform, focusing on production versatility, potential vaccine delivery routes, and efficacy for inducing an immune response in mice. In Phase II, they will investigate the broader potential of MicroCubes as a generic vaccine platform that can be used to deliver a wide range of antigens, and will use it to develop a candidate vaccine against HIV.

Prevention of Visceral Leishmaniasis Disease in Asymptomatic VL Patients

Dinesh MondalInternational Centre for Diarrhoeal Disease Research, BangladeshDhaka, Bangladesh
Grand Challenges Explorations
Infectious Diseases
1 May 2009

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.

Reducing Risk of ALRI by Improving Indoor Air Pollution

Golam RabbaniInternational Centre for Diarrhoeal Disease Research, BangladeshDhaka, Bangladesh
Grand Challenges Explorations
Infectious Diseases
1 May 2009

Golam Rabbani of International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) will study the effects that a new model of indoor cooking stove with concealed combustion chambers and ventilation chimney has in reducing indoor air pollution and subsequently, reducing acute lower respiratory infections and TB in children.

Large-Scale MHC Epitope Analysis for Vaccine Development

Gustavo Fioravanti VieiraUniversidade Federal do Rio Grande do SulPorto Alegre, Rio Grande do Sul, Brazil
Grand Challenges Explorations
Infectious Diseases
1 May 2009

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.

Increasing Vaccination Efficacy with ACE Inhibitors

Julio ScharfsteinUniversidade Federal do Rio de JaneiroRio de Janeiro, Rio de Janeiro, Brazil
Grand Challenges Explorations
Infectious Diseases
1 May 2009

Julio Scharfstein of Universidade Federal do Rio de Janeiro in Brazil will study whether a pre-dose of captopril, an established angiotensin-converting enzyme (ACE) inhibitor and anti-hypertension drug, can increase the potency of vaccines by increasing the activation of dendritic cells.

Immune Reinforcing Attenuated Whole-Sporozoite as Vaccine

Guang-hong TanHainan Provincial Key Laboratory of Tropical MedicineHaikou, China
Grand Challenges Explorations
Vaccines
1 May 2009

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.

Generation of Influenza-Resistant Chicken by Triple Combination Lentiviral Vector-mediated Genetic Modification

Chen YangchaoThe Chinese University of Hong KongHong Kong, China
Grand Challenges Explorations
Infectious Diseases
1 May 2009

Chen Yangchao of the Chinese University of Hong Kong proposes developing a lentiviral vector that targets the entry and replication of influenza viruses in domestic chickens. The team plans to test the ability of these modified chickens to be resistant to various influenza viruses in an effort to reduce the frequency of flu epidemics in poultry and, ultimately, in humans.

Vaccine Discovery by Mapping Quasi-species Sequence Space

Marco VignuzziInstitut PasteurParis, France
Grand Challenges Explorations
Infectious Diseases
1 May 2009

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.

Rapid Urine-Based Dipstick Test for Diagnosis of Malaria

Uri McKakpoUniversity of GhanaAccra, Ghana
Grand Challenges Explorations
Malaria Eradication
1 May 2009

Uri Selome McKakpo of the University of Ghana will develop and test a rapid dipstick test that utilizes monoclonal antibodies to detect parasite antigens present in urine of infected individuals. Using this technology, the team hopes to create a new diagnostic test for malaria that requires minimal training to use and does not depend on invasive blood samples.

How to Break B Tolerance and Induce HIV-Protective Antibodies to CCR5

Lucia LopalcoSan Raffaele Scientific InstituteMilano, Italy
Grand Challenges Explorations
Vaccines
1 May 2009

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.

Host Targets in Mtb Infection

Nigel SavageLeiden University Medical CenterLeiden, Netherlands
Grand Challenges Explorations
Drug Resistance
1 May 2009

Because tuberculosis manipulates host cells to resist the immune response and current drug therapies, Nigel Savage of Leiden University Medical Center in the Netherlands will utilize RNAi analysis to identify the essential pathways used by the bacteria to modify its host cell. By discovering these pathways, novel therapies can be developed to counteract this host manipulation without directly targeting the pathogen and causing the development of resistance.

Robotic Health Assistant for Rational Management of Fevers among Nomads

Oladele AkogunCommon Heritage FoundationJimeta-Yola, Nigeria
Grand Challenges Explorations
Drug Resistance
1 May 2009

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.

A Novel Way of Targeting TB using Aptamers and Nanotechnology

Boitumelo SemeteCouncil for Scientific and Industrial ResearchPretoria, South Africa
Grand Challenges Explorations
Drug Resistance
1 May 2009

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.

Development of Indoor Spray to Control Malaria Transmission

Walter FockeUniversity of PretoriaPretoria, South Africa
Grand Challenges Explorations
Malaria Eradication
1 May 2009

Because DDT is the only insecticide that remains effective for more than a year, Walter Focke of the University of Pretoria in South Africa will investigate how insecticides degrade when applied on an indoor surface. Focke will then study whether combining the insecticide with paint to create a “whitewash” can mitigate this disintegration and enhance stability.

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