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.

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.

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.

Reto Brun (Swiss Tropical and Public Health Institute) and Isabel Roditi (University of Bern) in Switzerland seek to identify small molecules that prematurely induce African trypanosomes, which are parasites that cause fatal sleeping sickness, to differentiate into the life stages necessary for transmission of the parasite. Forcing this transformation within the mammalian host could be the basis for new methods to kill trypanosomes, and this concept might be applied to other vector-borne disease . In this project’s Phase I research, Brun and Roditi developed a whole-cell assay to identify small molecules that stimulate early differentiation of African trypanosomes. In Phase II, they will perform high-throughput screens for such small molecules, validate active molecules in a suite of assays, and study them in a mouse model of infection.

Melody Swartz and Jeffrey Hubbell of the Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland, will explore the use of a robust and inexpensive nanotechnology, which may penetrate lymph tissue to more effectively trigger immune responses, as a new tool for prevention of TB.

Luke Savage and Dave Newman led engineers at Exeter University in the United Kingdom in a program to develop a handheld, inexpensive battery-powered instrument that can rapidly diagnose malaria. By using magneto-optics to detect the hemozoin crystals produced as a byproduct of malaria parasite digestion of hemoglobin in the red blood cell, they avoid relying on invasive blood sampling. The project's Phase I research produced a robust hand-held diagnostic device able under laboratory conditions to detect malarial infection at well below 100 parasitized red blood cells per microliter in less than two minutes. In Phase II, simpler yet improved second generation devices will undergo further development and clinical testing under field conditions until they can meet the sensitivity and specificity standards required of a test for malaria.

One hypothesis of why protective immunity to HIV in the general population is very low is that the virus can exist in a hidden form in the body and can mutate very quickly to escape immune destruction. George Dickson of Royal Holloway University of London will design and evaluate so-called "infinite-epitope" vaccines for their potential to provide simultaneous and broad protective immunity to the many variant forms of HIV.

Marcus Horwitz and colleagues at UCLA in the U.S. will develop and test a novel drug delivery system in which nanoparticles loaded with anti-TB drugs selectively target macrophages, and release the drugs intracellularly via a pH-dependent gate, allowing delivery of high concentrations on antibiotics into the host cells for Mycobacterium tuberculosis.

Antimicrobial peptides (AMPs) are essential components of the innate immune system that provides resistance to a variety of pathogenic organisms by selectively lysing, or bursting, cellular membranes of invading pathogens. Doron Greenbaum of the University of Pennsylvania in the U.S. will test whether small molecules that mimic the natural AMPs can selectively kill the parasite that causes malaria. Such an approach could reduce costs of production as well as limit the emergence of drug resistance.

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.

To test the theory that certain metabolic pathways essential to the survival of bacteria are immutable and therefore promising targets of drug therapy, Krishna Kodukula and colleagues at SRI International in the U.S. will identify peptides that bind key metabolites of M. tuberculosis, and test their ability to kill the bacteria.

Larry Walker of the University of Mississippi in the U.S. will test an innovative approach to mitigate the toxicity of primaquine, a promising and powerful malaria drug. Walker will separate the drug into two components, called isomers, to see if a single form retains the ability to eliminate the malaria parasite in its latent liver stages and the mature gametocytes while reducing toxic side effects.

Guirong Wang and colleagues at Vanderbilt University in the U.S. have recently identified key sensory heat receptors used by mosquitoes to target hosts. Wang will use these proteins as molecular targets to develop insect repellents and masking agents that block or hyper-stimulate these receptors and reduce the ability of the vectors to find hosts and spread disease.

Jefferson Vaughan of the University of North Dakota will seek to augment zooprophylaxis, the practice of using livestock to divert mosquito blood feeding away from humans, by developing an anti-mosquito vaccine for cattle that kill the insect before they bite humans.

Little is known about the role taste plays in the mosquito feeding process. Paul Breslin of the Monell Chemical Sense Center in the U.S. will test the sensitivity of the mosquito taste system to human skin compounds in an effort to identify key compounds that cue the insects to accept or reject blood meals from humans.

Kasturi Haldar of the University of Notre Dame in the U.S. will rapidly screen malaria parasite genes that are essential for invasion and growth in human red blood cells. Characterizing these proteins may reveal novel vaccine targets for blood stage infection.