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.

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.

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.

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.

Mark Blumberg from the University of Iowa in the U.S. will develop a method to record and analyze twitching during infant sleep as a non-invasive measure of early brain development. Muscle twitching during REM sleep is known to reflect nervous system function. They hypothesize that it also shapes the developing brain, and could be used to diagnose future neurodevelopmental disorders. They will position miniature accelerometers, which measure physical activity, on the limbs and heads of 16 full-term and 16 preterm infants, and measure the quantity and pattern of muscle twitching biweekly during sleep from age 3-4 months, and then at 6, 9 and 12 months. They will also design analytical tools to interpret the datasets. The goal is a simple, inexpensive, early neurological assessment method that can also be used in low-resource settings.

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.

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.

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.

Robert Habib of the American University of Beirut in Lebanon will determine whether measuring the patterns of heart rate and breathing rate over time in infants reflects the maturity of the autonomous nervous system and thereby the extent of brain development. The autonomous nervous system controls complex physiological rhythms such as the variability of heart rate over time. These rhythms can be measured non-invasively and will be compared between ten full-term and ten preterm infants measured at birth and every six weeks until 56 weeks, and under different stimulating conditions. A low-cost and simple method to collect the physiological data will also be explored.

Thokozani Mwenyekonde from CARE in Malawi is implementing the Umodzi project to promote gender equality for women and girls by engaging adolescent girls and boys, along with supportive adult male and female role models, to integrate gender equitable attitudes and behavior in schools as a basis for changing attitudes nationwide. Umodzi, which means "oneness" in the local Chichewa language, will build upon and adapt existing gender equality approaches including integrating efforts into the school curriculum, training teachers who convene teen club meetings, and working with adults who are also engaged in CARE's pro-women agriculture and savings programs in the school catchment areas.

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.

Ofer Levy at Children's Hospital Boston in the U.S. will determine whether synthetic molecules called imidazoquinolines activate newborns' white blood cells, and could be used as candidate vaccine adjuvants to dramatically enhance immunization at birth. In this project's Phase I research, Levy demonstrated that Toll-like Receptor-7 and -8 agonists are superior to agonists of other Toll-like receptors and to alum, an already approved vaccine adjuvant, in activating newborn immune responses in studies in vitro. In Phase II, Levy will conduct in vivo studies to test the ability of these molecules to boost vaccine responses, evaluating both the safety and efficacy of this approach.